Weigelt et al - SupplementaryMethods - Re-Revised-clean · ‘centroids’ for each SSP included in this study ... updated Unigene cluster IDs were used to annotate each centroid/SSP

Supplementary webappendixThis webappendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors.

Supplement to: Weigelt B, Mackay A, A’hern R, et al. Breast cancer molecular profiling with single sample predictors: a retrospective analysis. Lancet Oncol 2010; published online Feb 23. DOI:10.1016/S1470-2045(10)70008-5.

Webappendix Supplementary Methods HER2 immunohistochemistry and fluorescence in situ hybridisation Immunohistochemistry for HER2 of the 53 grade III invasive ductal carcinomas was performed as previously described1, and scored according to the ASCO/CAP guidelines2. Cases displaying a 3+ score were considered positive; for cases displaying a 2+ score the HER2 gene status was confirmed by fluorescence in situ hybridisation (FISH) tested with an FDA approved method (Vysis, Inc, Downers Grove, IL, USA) as previously described3. Background molecular subtype assignment The methodology described for classification of single samples into one of the five molecular subtypes is based on the use of a single sample predictor (SSP). Single sample predictors are based on the correlations between a given case and the molecular subtype ‘centroids’4. The ‘centroids’ are profiles consisting of the average gene expression for each of the genes of a given SSP (i.e. Sorlie et al’s SSP4, Hu et al’s SSP5 and Parker et al’s SSP6) in each of the five molecular subtype classes. The five ‘centroids’ for each SSP included in this study (i.e. Sorlie et al’s SSP4, Hu et al’s SSP5 and Parker et al’s SSP6) were computed and made public available by the proponents of the molecular taxonomy4-6. For the classification of a given tumour using a SSP, the correlation to each of the five ‘centroids’ (i.e. basal-like, HER2, luminal A, luminal B and normal breast-like) is determined. The ‘centroid’ that has the highest correlation with a given sample determines its molecular subtype class (i.e. ‘nearest centroid’). In addition, Sorlie et al4 proposed and applied a more conservative approach, and classified only those tumours that showed a correlation of >0.1 with any of the five centroids and regarded tumours with a correlation of <0.1 as ‘unclassified’. Microarray analysis Analyses were performed in R version 2.9.0 (http://cran.rproject.org/). Annotated datasets, centroid/SSP gene lists and the R code used for centroid correlations are available at http://rock.icr.ac.uk/collaborations/Mackay/. In addition, a supplementary sweave document of all codes used in this study is provided (please see webappendix Supplementary Sweave Document). Probe annotations and gene mapping of centroid/SSP gene lists To overlay the centroid/SSP gene lists with the genes/probes of the microarrays from the different breast cancer cohorts, the annotations of centroid/SSP gene lists and breast cancer datasets were comprehensively updated and mapped to build 36 of the human genome (Ensembl assembly 54). Different types of gene identifiers (IDs), including HUGO gene symbols, Ensembl gene IDs and updated Unigene cluster IDs were used to annotate each centroid/SSP gene list and breast cancer dataset. The centroids/SSPs have generally been reported and annotated with Unigene cluster IDs4,5. With each build of the Unigene database, however, UniGene clusters may be split into other clusters creating new Unigene IDs or may be retired. This results in probes on each microarray platform that carry multiple Unigene IDs, making unambiguous 1:1 matching of probes, genes and Unigene IDs challenging. In order to address this problem, we updated each of the centroid/SSP gene lists and datasets used with updated Unigene annotation from build 218. Methodologies such as calculation of centroid/SSP correlations, which rely on the overlay of features between different microarray platforms and datsets, are more accurate and consistent if an ID more stable than Unigene cluster is chosen for the overlay. The genes of the centroids/SSPs published by Sorlie et al4, Hu et al5 and Parker et al6 were retrieved from the Stanford Microarray Database (http://smd.stanford.edu/) or University of North Carolina Microarray Database (https://genome.unc.edu/cgi-bin/SMD/umad.pl). IMAGE clone IDs of the 500 gene centroids/SSPs by Sorlie et al4 were updated and annotated using SOURCE (http://smd.stanford.edu/cgi-bin/source/sourceSearch) and merged with Ensembl gene IDs using Entrez gene numbers. HUGO gene symbols, Unigene and Ensembl IDs for the 306 gene centroids/SSPs by Hu et al5 were retrieved directly from Biomart (www.ensembl.org/biomart/index.html) using the Agilent probe IDs supplied by the authors5. The 50 gene centroids/SSPs (PAM50) described by Parker et al6 were annotated using SOURCE as described above based upon the HUGO gene symbols described in the supplementary information supplied by the authors6. The probes/unique genes identified for each centroid/SSP gene list and breast cancer

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dataset using HUGO gene symbols, Ensembl gene IDs and Unigene cluster IDs can be found in webappendix supplementary table 15. Probe annotations and gene mapping of breast cancer datasets The gene expression data of the cohort of 53 grade III invasive ductal carcinomas published previously by Natrajan et al 1,7 are publicly available at ArrayExpress (E-TABM-543). Raw gene expression values were subjected to variance stabilisation transformation (lumiT) and were robust-spline normalised (lumiN) using the Bioconductor lumi package (1.8.3) in R (http://www.bioconductor.org/packages/2.3/bioc/html/lumi.html)7. Data were not background subtracted. Quality control of a LumiBatch object was performed using the Bioconductor lumi package, which included estimation of the mean and standard deviation of the chips, detectable probe ratio of each chip, sample (chip) relations, and detection of outliers of samples (chips). Log2 intensity values were used as expression data for further analyses. The gene expression data of the 53 grade III invasive ductal carcinomas were annotated using the Bioconductor lumi package in R based upon the annotation library lumiHumanAll.db (1.6.1). HUGO gene symbol, Unigene and Ensembl ID annotations of the Illumina Human WG6 v2 microarray based upon ILMN identifier were retrieved from Ensembl using Biomart. All annotations were merged in R. For analysis of the breast cancer datasets from public resources, the publicly available normalised gene expression data as well as clinical data of the ‘NKI-295’8 (n=295; http://microarray-pubs.stanford.edu/wound_NKI/explore.html), ‘Wang’9 (n=286;GEO, accession number GSE2034) and ‘TransBig’10 (n=198; GEO, accession number GSE7390) cohorts were retrieved. Gene annotations of these breast cancer datasets were updated based upon the individual probe identifier on each array used in the different studies to the current build of the genome NCBI36 Ensembl assembly 54 and Unigene build 218 using SOURCE, BioMart and Matchminer (http://discover.nci.nih.gov/matchminer/index.jsp). Annotation of the U133A Affymetrix probe IDs to Ensembl gene IDs for the ‘Wang’9 and ‘TransBig’10 datasets were retrieved directly from Ensembl assembly 54 using Biomart and merged with the publicly available array data supplied by the authors. The data for the ‘NKI-295’ breast cancers8 were retrieved from the supplementary data published by Chang et al.11 The ‘Phil Green contig accession numbers’ and ‘Systemic Name’ supplied by the authors were used as source of accession numbers to retrieve the HUGO gene symbol, Unigene cluster and Ensembl IDs using SOURCE, Biomart and R as described above. Datasets were then filtered for identifiers present in each centroid gene list using HUGO gene symbol, Unigene cluster and Ensembl gene IDs. Molecular subtype assignment using centroids/ SSPs According to the methodology described for classification of single tumour samples into one of the five molecular subtypes (see ‘Background molecular subtype assignment’ above), the molecular subtypes of each case was assigned based on the nearest of the five centroids/SSPs. Correlations to the 500 gene centroids/SSPs by Sorlie et al4,11 were determined using Pearson correlation, to the 306 gene centroids/SSPs by Hu et al5 and 50 gene centroids/SSPs by Parker et al6 using Spearman rank correlation. The nearest centroid for each tumour to each of the centroids/SSPs was recorded, and separately, cases that did have a correlation <0.1 to any centroid were recorded as ‘unclassified’ as described previously by Sorlie et al4. It should be noted that for the process of molecular subtype assignment using centroids/SSPs, additional parameters and procedures were not described in sufficient detail in the original publications4-6. To minimise the need to make assumptions on methodology for the assignment of molecular subtypes and to minimise inconsistencies in the analysis methods, we first sought to reproduce the molecular subtype assignments of the ‘NKI-295’8 breast cancers previously classified by the proponents of the molecular subtypes using the SSPs by Sorlie et al4 or the SSP by Hu et al5 (webappendix supplementary table 2). We tested different methods of annotating centroids/SSPs and datasets for overlay, and probe handling. We calculated the correlation of each tumour with the SSP by Sorlie et al4, by Hu et al5 or by Parker et al6 using genes common to each dataset and centroids/SSPs based upon different gene annotations used for mapping of the centroid/SSP gene lists and breast cancer datasets, including HUGO gene symbol, Ensembl and Unigene cluster IDs. In addition, if

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multiple probe IDs were identified to match a gene in the published gene centroid/SSP lists, we used either all probes or averaged probes with the same identifier to avoid weighting of genes represented by multiple probes, similar to the computation/ creation of the centroids/SSPs as previously described4,5. We observed that the agreement between the molecular subtype assignment of the ‘NKI-295’8 tumours using the Sorlie et al4 or Hu et al5 SSPs as published previously by Chang et al11 and Fan et al12, respectively, and between the methods tested here was dependent on the methodology employed, with Kappa scores 0.715 to 0.940 (see webappendix supplementary table 3). The agreement was dependent on i) the gene identifier employed for annotating and overlaying of centroid/ SSP gene lists and datasets, ii) the use of all probes identifying a gene vs averaging of multiple probes representing the same gene to determine correlations to a centroid/ SSP, and iii) the inclusion/ exclusion of cases with a weak correlation to a centroid/ SSP class (cut-off <0.1 as described by Sorlie et al4) (see webappendix supplementary table 3). The method that most accurately reproduced with an ‘almost perfect’ Kappa score the previously published molecular subtype assignments of the ‘NKI-295’ breast cancers11,12 using the Sorlie et al4 SSP and the Hu et al5 SSP as published by Chang et al11 and Fan et al12, respectively (KS of 0.912 (95% CI 0.875 – 0.949) and 0.897 (95% CI 0.896 – 0.938) for the Sorlie et al4 and Hu et al5 SSPs, respectively; webappendix supplementary table 3), was HUGO gene symbols for annotation and mapping of centroid/SSP gene lists and breast cancer datasets, and averaging of multiple probes identifying a gene in a centroid/SSP gene list. This method, therefore, was chosen to define the molecular subtypes in subsequent analyses in our study. ESR1, PGR, ERBB2, GRB7, AURKA and MKI67 mRNA expression levels To estimate the activation of oestrogen-receptor (ER) signalling, HER2 signalling and proliferation in the different molecular subtypes of breast cancer (i.e. basal-like, luminal A, luminal B, HER2 and normal breast-like), the average mRNA expression levels of ESR1 and PGR (surrogates for ER signalling), ERBB2 and GRB7 (genes related to the HER2 amplicon), and AURKA and MKI67 (surrogates for proliferation) for each sample in each of the four breast cancer datasets were extracted from the processed and normalised gene expression datasets used for the SSP analysis as described above. If multiple probes were identified to match a gene, probes with the same identifier were averaged. The average mRNA expression levels of ESR1, PGR, ERBB2, GRB7, AURKA and MKI67 in each of the molecular subtypes assigned using Sorlie et al4, Hu et al5 or Parker et al6 SSPs in each of the four breast cancer datasets were presented as box and whisker plots, with the error bars representing the standard deviation of mean. Supplementary References 1. Natrajan R, Lambros MB, Rodriguez-Pinilla SM, et al. Tiling path genomic profiling of grade 3 invasive ductal breast cancers. Clin Cancer Res 2009;15(8):2711-22. 2. Wolff AC, Hammond ME, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 2007;25(1):118-45. 3. Marchio C, Lambros MB, Gugliotta P, et al. Does chromosome 17 centromere copy number predict polysomy in breast cancer? A fluorescence in situ hybridization and microarray-based CGH analysis. J Pathol 2009;219(1):16-24. 4. Sorlie T, Tibshirani R, Parker J, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A 2003;100(14):8418-23. 5. Hu Z, Fan C, Oh DS, et al. The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics 2006;7:96. 6. Parker JS, Mullins M, Cheang MC, et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol 2009;27(8):1160-7. 7. Natrajan R, Weigelt B, Mackay A, et al. An integrative genomic and transcriptomic analysis reveals molecular pathways and networks regulated by copy number aberrations in basal-like, HER2 and luminal cancers. Breast Cancer Res Treat 2009:epub ahead of print. 8. van de Vijver MJ, He YD, van't Veer LJ, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 2002;347(25):1999-2009.

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9. Wang Y, Klijn JG, Zhang Y, et al. Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet 2005;365(9460):671-9. 10. Desmedt C, Piette F, Loi S, et al. Strong time dependence of the 76-gene prognostic signature for node-negative breast cancer patients in the TRANSBIG multicenter independent validation series. Clin Cancer Res 2007;13(11):3207-14. 11. Chang HY, Nuyten DS, Sneddon JB, et al. Robustness, scalability, and integration of a wound-response gene expression signature in predicting breast cancer survival. Proc Natl Acad Sci U S A 2005;102(10):3738-43. 12. Fan C, Oh DS, Wessels L, et al. Concordance among gene-expression-based predictors for breast cancer. N Engl J Med 2006;355(6):560-9.

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Cohort Reference Number of samples

RNA extraction method

Data acquisition microarray platform

Quality control parameters and data processing

Normalisation method

1 53 grade III IDC-NSTs Natrajan R et al, Breast Cancer Res Treat 2009 53 Trizol Illumina Human WG6 V2 Bioconductor lumi package Variance stabilisation transformation and robust spline normalisation using

the Bioconductor lumi package.

2 NKI-295 van de Vijver MJ et al, N Engl J Med 2002 295 RNAzolB Hu25k Agilent Rosetta 2 colour Loess Rosetta. Normalisation between the channels accomplished

by normalising each channel to the mean intensities of all genes.

3 Wang Wang Y et al, Lancet 2005 286 RNAzolB Affymetrix U133A Affymetrix packageMAS5 using the Affymetrix package. For chip normalisation, probe sets

were scaled to a target intensity of 600, and scale mask files were not selected.

4 TransBig Desmedt C et al, Clin Cancer Res 2007 198 RNAzolB Affymetrix U133A Affymetrix package

MAS5 using the Affymetrix package. For chip normalisation, probe sets were scaled to a target intensity of 600, and scale mask filters were not

selected.

Supplementary Table 1: Details of the sample size of each cohort, RNA extraction, data acquisition microarray platform, quality control parameters and data processing and normalisation method.

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Sample ID

SSP Sorlie et al 2003 (published by Chang et al 2005)

SSP Sorlie et al 2003; cut-off correlation with subtype <0.1 (published by Chang et al 2005)

SSP Hu et al 2006 (published by Fan et al 2006)

4 Luminal B Luminal B Luminal B

6 Luminal A Luminal A Luminal A

7 Normal breast-like UC Normal breast-like

8 Basal-like Basal-like Basal-like

9 Luminal A UC Luminal A

11 Luminal B Luminal B HER2


13 Luminal B UC Luminal B



26 Luminal B UC Luminal A

27 Normal breast-like Normal breast-like Luminal A

28 Normal breast-like Normal breast-like Normal breast-like





45 Luminal A Luminal A Luminal B



56 Normal breast-like UC Luminal A




60 HER2 HER2 Luminal A


62 HER2 HER2 HER2





76 HER2 HER2 Basal-like



109 HER2 HER2 HER2



113 HER2 UC Normal breast-like









127 Luminal A UC Luminal B



130 HER2 HER2 HER2



133 HER2 UC Luminal A



136 HER2 HER2 HER2



139 Luminal B Luminal B Luminal A


141 HER2 HER2 HER2

142 Luminal B Luminal B Normal breast-like




147 HER2 HER2 HER2


149 HER2 HER2 HER2


151 Luminal B Luminal B Basal-like

153 HER2 HER2 HER2





158 HER2 HER2 HER2


























187 Basal-like Basal-like Normal breast-like










Supplementary Table 2: Molecular subtype classification of ‘NKI-295’ 8 breast cancers made using the single sample predictors by Sorlie et al4 or by Hu et al5 as published previously11,12 and their agreement.

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197 HER2 HER2 Normal breast-like


199 HER2 HER2 HER2







208 HER2 HER2 HER2

209 Luminal B UC Normal breast-like

210 HER2 HER2 HER2





217 HER2 HER2 HER2








227 Normal breast-like UC Luminal B















246 HER2 HER2 HER2



249 HER2 HER2 HER2


251 HER2 HER2 HER2




257 HER2 HER2 HER2





263 Basal-like UC Luminal A










273 HER2 HER2 Luminal B












286 HER2 HER2 HER2


288 HER2 HER2 HER2


291 Normal breast-like UC Luminal B
















308 HER2 HER2 HER2























7


333 HER2 HER2 HER2








341 HER2 HER2 HER2














355 Luminal B Luminal B Normal breast-like














369 HER2 HER2 HER2

370 Luminal A Luminal A Normal breast-like




375 HER2 HER2 HER2













392 HER2 HER2 HER2











Agreement with assignment by Sorlie et al SSP: 188/295 cases; Kappa score 0.527 (95% Confidence interval 0.456-0.597); Agreement with assignment by Sorlie et al SSP, exclusion of cases with cut-off correlation <0.1: 135/186 cases; Kappa score 0.646 (95% Confidence interval 0.565-0.727). SSP: single sample predictor; UC: unclassified.

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Sample IDMolecular Subtypes

published by Chang et al, PNAS 2005

Molecular Subtypes published by Chang et al, PNAS 2005,

cut-off correlation <0.1

HUGO symbol, probe average,

Pearson correlation

HUGO symbol, probe average, Pearson correlation,

cut-off correlation <0.1

HUGO symbol, all probes, Pearson

correlation

HUGO symbol, all probes, Pearson correlation, cut-off

correlation <0.1

Ensembl IDs, probe average, Pearson

correlation

Ensembl IDs, probe average, Pearson correlation, cut-off

correlation <0.1

Unigene IDs, probe average, Pearson correlation

Unigene IDs, probe average, Pearson correlation (cut-off

correlation <0.1)Sample ID

Molecular Subtypes published by Fan et

al, NEJM 2006

HUGO symbol, probe average, Spearman

correlation

HUGO symbol, probe average, Spearman correlation, cut-off

correlation <0.1

HUGO symbol, all probes, Spearman

correlation

HUGO symbol, all probes, Spearman correlation, cut-off

correlation <0.1

Ensembl IDs, probe average, Spearman

correlation

Ensembl IDs, probe average, Spearman correlation, cut-off

correlation <0.1

Unigene IDs, probe average, Spearman

correlation )

Unigene IDs, probe average, Spearman correlation, cut-off

correlation <0.1

Agreement with published molecular subtype assigment by Chang et al

275/295 cases Kappa score 0.912




Agreement with published molecular subtype assigment by Fan et al





Agreement with published molecular subtype assigment by Chang et al excluding UCs, cut-

off <0.1





Agreement with published molecular subtype assigment by Fan et al

excluding UCs, cut-off <0.1





Agreement with published molecular subtype assigment by Chang et al including UCs, cut

off <0.1





4 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 4 Luminal B HER2 UC Luminal B UC HER2 UC HER2 UC6 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 6 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A7 Normal breast-like UC Normal breast-like UC Normal breast-like UC Normal breast-like UC Normal breast-like UC 7 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like8 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 8 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like9 Luminal A UC Luminal A UC Luminal A UC Luminal A Luminal A Luminal A UC 9 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A

11 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 11 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER212 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 12 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like13 Luminal B UC Luminal B UC Luminal B UC Luminal B UC Luminal B UC 13 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B14 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 14 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A17 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 17 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A26 Luminal B UC Luminal B UC Luminal B UC Luminal B UC Luminal B UC 26 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A27 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like 27 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A28 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like 28 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like29 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like 29 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like36 Luminal A UC Luminal A UC Luminal A UC Luminal A UC Luminal A UC 36 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A38 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 38 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A39 Luminal B UC Luminal B UC Luminal B UC Luminal B UC Luminal B UC 39 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A45 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 45 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B48 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 48 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like51 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 51 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A56 Normal breast-like UC Normal breast-like UC Normal breast-like UC Luminal A UC Normal breast-like UC 56 Luminal A Luminal A Luminal A Luminal A UC Luminal A Luminal A Luminal A Luminal A57 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 57 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like58 Luminal B UC Luminal B UC Luminal B UC Luminal B UC Luminal B UC 58 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B59 Luminal B UC Luminal B UC Luminal B UC Luminal B Luminal B Luminal B UC 59 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B60 HER2 HER2 HER2 HER2 HER2 HER2 HER2 UC HER2 HER2 60 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A61 Luminal B UC Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 61 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A62 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 62 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER271 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 71 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like72 Luminal A UC Luminal A UC Normal breast-like UC Luminal A UC Luminal A UC 72 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A73 Normal breast-like Normal breast-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 73 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like75 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 75 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like76 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 76 Basal-like Basal-like Basal-like Basal-like Basal-like HER2 HER2 Basal-like Basal-like

103 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 103 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like107 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 107 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B109 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 109 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2110 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 110 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B111 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 111 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2113 HER2 UC HER2 UC HER2 UC HER2 UC HER2 UC 113 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like117 Luminal B UC Luminal B UC Luminal B UC Luminal B UC Luminal B UC 117 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A118 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 118 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A120 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 120 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A122 Luminal A UC Luminal A UC Luminal A UC Luminal A Luminal A Luminal A UC 122 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A123 Luminal A UC Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 123 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A124 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 124 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A125 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 125 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A126 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 126 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal A Luminal A127 Luminal A UC Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 127 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B128 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 128 Luminal B Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B Luminal A Luminal A129 Luminal B UC Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 129 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A130 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 130 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2131 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 131 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like132 Luminal B UC Luminal B UC Luminal B UC Luminal B UC Luminal B UC 132 Luminal B Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B Luminal A Luminal A133 HER2 UC HER2 UC HER2 UC HER2 UC HER2 UC 133 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A134 HER2 UC HER2 UC HER2 UC Normal breast-like UC HER2 UC 134 Normal breast-like Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A135 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 135 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like136 HER2 HER2 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 136 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2137 Normal breast-like UC Luminal A UC Luminal A UC Luminal A UC Luminal A UC 137 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A138 HER2 UC HER2 HER2 HER2 HER2 HER2 UC HER2 HER2 138 Normal breast-like Normal breast-like Normal breast-like Luminal A Luminal A Normal breast-like Normal breast-like Luminal A Luminal A139 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 139 Luminal A Luminal A UC Luminal A UC HER2 UC Luminal A Luminal A140 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 140 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A141 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 141 HER2 Basal-like Basal-like HER2 HER2 HER2 HER2 HER2 HER2142 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 142 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like144 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 144 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like145 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 145 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B146 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 146 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A147 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 147 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2148 Luminal A UC Luminal A UC Luminal A UC Luminal A Luminal A Luminal A UC 148 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A149 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 149 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2150 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 150 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B151 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 151 Basal-like Basal-like UC Basal-like UC Basal-like UC Basal-like UC153 HER2 HER2 HER2 HER2 HER2 HER2 HER2 UC HER2 HER2 153 HER2 HER2 UC Luminal B Luminal B Luminal B UC HER2 UC154 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 154 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A155 Luminal A UC Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 155 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A156 Normal breast-like UC Normal breast-like UC Normal breast-like UC Normal breast-like UC Normal breast-like UC 156 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A157 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 157 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A158 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 158 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2159 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 159 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A160 Normal breast-like UC Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like 160 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A161 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 161 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A162 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 162 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like163 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 163 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B164 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 164 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like165 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 165 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B166 Luminal A UC Luminal B UC Luminal B UC Luminal B UC Luminal B UC 166 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B167 Luminal A UC Luminal A UC Luminal A UC Luminal A UC Luminal A UC 167 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A169 Luminal A UC Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B Luminal A Luminal A 169 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A170 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 170 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A172 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 172 HER2 HER2 UC HER2 UC HER2 UC HER2 UC174 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 174 Luminal B Luminal B Luminal B Luminal B Luminal B HER2 UC Luminal B UC175 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 175 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like176 HER2 UC Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 176 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A177 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 177 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like178 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like 178 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Luminal A Luminal A Luminal A Luminal A179 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 179 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like180 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 180 Luminal B Luminal B Luminal B Luminal B Luminal B HER2 HER2 HER2 HER2181 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 181 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2182 Normal breast-like UC Normal breast-like UC Normal breast-like UC Normal breast-like Normal breast-like Normal breast-like UC 182 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like183 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 183 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A184 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 184 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like185 Luminal B UC Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 185 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A186 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 186 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like187 Basal-like Basal-like Normal breast-like Normal breast-like HER2 HER2 Normal breast-like Normal breast-like HER2 HER2 187 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like188 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 188 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A189 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 189 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like190 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 190 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A191 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 191 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A192 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 192 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B193 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 193 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A194 HER2 UC HER2 UC HER2 UC Normal breast-like UC HER2 UC 194 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like195 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 195 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like196 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like 196 Normal breast-like Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A197 HER2 HER2 HER2 HER2 HER2 HER2 Basal-like Basal-like HER2 HER2 197 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like198 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 198 Luminal A Luminal A UC Luminal A UC Luminal A UC Luminal A UC199 HER2 HER2 HER2 HER2 Luminal B Luminal B Luminal B Luminal B HER2 HER2 199 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2200 Normal breast-like UC Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like 200 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A201 Normal breast-like UC Normal breast-like UC Normal breast-like UC Normal breast-like UC Normal breast-like UC 201 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A202 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 202 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like203 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 203 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A205 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 205 Luminal A Luminal A UC Luminal A UC Luminal A UC Luminal A UC207 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 207 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A208 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 208 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2209 Luminal B UC Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 209 Normal breast-like Luminal B UC Luminal B UC Normal breast-like UC Normal breast-like UC210 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 210 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2212 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 212 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like213 Luminal B UC Luminal B UC Luminal B UC Luminal B UC Luminal B UC 213 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B HER2 HER2214 Luminal A UC Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 214 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A215 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 215 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like217 HER2 HER2 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 217 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2218 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 218 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B219 HER2 HER2 HER2 HER2 HER2 HER2 HER2 UC HER2 HER2 219 Normal breast-like Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A220 Normal breast-like UC Luminal A UC Luminal A UC Luminal A UC Luminal A UC 220 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A221 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 221 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A222 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 222 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like224 Luminal A UC Luminal A UC Luminal B UC Luminal A UC Luminal A UC 224 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A UC Luminal A UC226 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 226 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like227 Normal breast-like UC Normal breast-like UC Normal breast-like UC Luminal A UC Normal breast-like UC 227 Luminal B Luminal A Luminal A Luminal A Luminal A Luminal A UC Luminal A UC228 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 228 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like229 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 229 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2230 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 230 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like231 Luminal A UC Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 231 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A233 Luminal A UC Luminal A UC Luminal A UC Luminal A UC Luminal A UC 233 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A235 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 235 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A236 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 236 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2237 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 237 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like238 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 238 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like239 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 239 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A240 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 240 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B UC241 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 241 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like243 Normal breast-like UC Normal breast-like UC Normal breast-like UC Luminal B UC Normal breast-like UC 243 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A245 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 245 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like246 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 246 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2247 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 247 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A248 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 248 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like249 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 249 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2250 Normal breast-like UC Normal breast-like UC Normal breast-like UC Normal breast-like UC Normal breast-like UC 250 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A251 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 251 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2252 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 252 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B254 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 254 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A UC Luminal A Luminal A256 Normal breast-like UC Normal breast-like UC Normal breast-like UC Normal breast-like UC Normal breast-like UC 256 Normal breast-like Normal breast-like UC Normal breast-like Normal breast-like Normal breast-like UC Normal breast-like UC257 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 257 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2258 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 258 Normal breast-like Normal breast-like UC HER2 UC HER2 HER2 HER2 UC259 Normal breast-like UC Normal breast-like Normal breast-like Normal breast-like UC Normal breast-like Normal breast-like Normal breast-like Normal breast-like 259 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like260 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like 260 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like261 Luminal A UC Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 261 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A263 Basal-like UC Luminal B UC Luminal B UC Luminal B UC Luminal B UC 263 Luminal A Luminal A UC Luminal A UC Normal breast-like UC Normal breast-like UC264 Luminal A UC Luminal A UC Luminal A Luminal A Luminal A UC Luminal A UC 264 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A265 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 265 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like266 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 266 Luminal A Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B Luminal A Luminal A267 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 267 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2268 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 268 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like269 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 269 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like270 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 270 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like271 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 271 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A272 Luminal A UC Luminal A UC Luminal A UC Luminal A UC Luminal A UC 272 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A273 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 273 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B274 Luminal A UC Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 274 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A275 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 275 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A276 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 276 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like277 Luminal B UC Luminal A UC Luminal A UC Luminal A Luminal A Luminal A UC 277 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A278 Normal breast-like UC Normal breast-like UC Normal breast-like UC Normal breast-like UC Normal breast-like UC 278 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A280 Normal breast-like UC Normal breast-like UC Normal breast-like UC Luminal A Luminal A Normal breast-like UC 280 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A281 Normal breast-like UC Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like 281 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A282 Normal breast-like UC Normal breast-like UC Normal breast-like UC Normal breast-like UC Normal breast-like UC 282 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A283 Luminal B UC Luminal A UC Luminal A UC Luminal A Luminal A Luminal A UC 283 Luminal B Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B284 Luminal B UC Luminal A UC Luminal A UC Luminal A Luminal A Luminal A UC 284 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B285 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 285 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A286 HER2 HER2 HER2 HER2 HER2 HER2 Luminal B Luminal B HER2 HER2 286 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2287 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 287 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A288 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 288 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 UC290 Luminal A UC Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 290 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A291 Normal breast-like UC Normal breast-like UC Normal breast-like UC Normal breast-like UC Normal breast-like UC 291 Luminal B Basal-like UC Basal-like UC Luminal B UC Basal-like UC292 Luminal B UC Luminal B UC Luminal B UC Luminal B UC Luminal B UC 292 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A293 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 293 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A294 Luminal B UC Luminal B UC Luminal B UC Luminal A UC Luminal B UC 294 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B295 Luminal B UC Luminal B UC Luminal A UC Luminal A UC Luminal A UC 295 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A296 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 296 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B HER2 HER2297 Luminal A UC Luminal A UC Luminal A UC Luminal A Luminal A Luminal A UC 297 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B298 Luminal B UC Luminal A UC Luminal A UC Luminal A UC Luminal A UC 298 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A300 Luminal B Luminal B Luminal B Luminal B Luminal B UC Luminal B Luminal B Luminal B Luminal B 300 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A301 Luminal A UC Luminal A UC Luminal A UC Luminal A Luminal A Luminal A UC 301 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A302 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 302 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A303 Luminal B UC Luminal A UC Luminal A UC Luminal A UC Luminal A UC 303 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A304 HER2 UC HER2 UC HER2 UC Normal breast-like UC HER2 UC 304 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like305 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 305 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A306 Luminal B UC Luminal B UC Luminal B UC Luminal A UC Luminal B UC 306 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A307 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 307 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like308 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 308 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2309 Luminal B UC Luminal B UC Luminal B UC Luminal A UC Luminal B UC 309 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A310 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 310 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like311 Luminal B UC Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B Luminal B Luminal B 311 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B312 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 312 Luminal B Luminal A UC Luminal B UC HER2 UC Luminal B UC313 Luminal B UC Luminal B UC Luminal B UC Luminal B Luminal B Luminal B UC 313 Normal breast-like Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A314 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 314 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B315 Luminal A UC Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 315 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A317 Luminal B UC Luminal B UC Luminal B UC Luminal B UC Luminal B UC 317 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B318 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 318 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A319 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 319 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2320 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 320 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like321 HER2 HER2 HER2 HER2 HER2 HER2 Luminal B UC HER2 HER2 321 Normal breast-like Luminal A Luminal A Luminal A Luminal A Normal breast-like Normal breast-like Normal breast-like Normal breast-like322 Luminal A Luminal A Luminal A UC Luminal A UC Luminal B UC Luminal A UC 322 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B323 Luminal A UC Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 323 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A324 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 324 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like325 Luminal B UC Luminal B UC Luminal B UC Luminal B UC Luminal B UC 325 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A326 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 326 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like327 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 327 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B328 Luminal A UC Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 328 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A329 Luminal B UC Luminal B UC Luminal B UC Luminal B Luminal B Luminal B UC 329 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B330 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 330 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like331 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 331 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B332 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 332 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like333 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 333 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2334 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 334 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A335 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 335 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like336 Luminal B UC Luminal B UC HER2 UC Luminal A UC Luminal B UC 336 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A337 Luminal A UC Luminal A UC Luminal A UC Luminal A Luminal A Luminal A UC 337 Luminal A Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B338 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 338 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like339 Luminal A UC Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 339 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B340 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 340 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B341 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 341 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2342 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 342 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B343 Luminal A UC Luminal A UC Luminal A UC Luminal A Luminal A Luminal A UC 343 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A344 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 344 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like345 Luminal A UC Luminal A UC Luminal A Luminal A Luminal A Luminal A Luminal A UC 345 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A346 Normal breast-like UC Normal breast-like UC Normal breast-like UC Normal breast-like UC Normal breast-like UC 346 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A347 Luminal B UC Basal-like UC Basal-like UC Basal-like UC Basal-like UC 347 Normal breast-like Luminal A UC Luminal A Luminal A Normal breast-like Normal breast-like Luminal A UC348 Luminal A UC Luminal A UC Luminal A UC Luminal A Luminal A Luminal A UC 348 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A349 Luminal B UC Luminal B UC Luminal B UC Luminal B UC Luminal B UC 349 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A350 Luminal B Luminal B Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 350 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like351 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 351 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2352 Luminal A UC Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 352 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A353 Luminal B UC Luminal B UC Luminal B UC Luminal A UC Luminal B UC 353 Luminal B Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A354 Luminal A UC Luminal A UC Luminal A UC Luminal A Luminal A Luminal A UC 354 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A355 Luminal B Luminal B Luminal B UC Luminal B UC Luminal B UC Luminal B UC 355 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like356 HER2 UC HER2 UC HER2 UC Luminal B UC HER2 UC 356 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A357 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like 357 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A358 Normal breast-like UC Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 358 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A359 Luminal B UC Luminal B UC Basal-like UC Luminal B UC Luminal B UC 359 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like360 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like 360 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A361 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like 361 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A362 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 362 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B363 Luminal A UC Luminal A Luminal A Luminal A UC Luminal A Luminal A Luminal A Luminal A 363 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B364 HER2 UC HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 364 Normal breast-like HER2 UC HER2 UC HER2 UC HER2 UC365 Luminal A UC Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 365 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A366 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 366 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A UC367 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 367 Basal-like Basal-like Basal-like Basal-like UC Basal-like Basal-like Basal-like Basal-like368 Luminal B UC Luminal B UC Luminal B UC Luminal B UC Luminal B UC 368 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Luminal A Luminal A Normal breast-like Normal breast-like369 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 369 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2370 Luminal A Luminal A Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like 370 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Luminal A Luminal A Normal breast-like Normal breast-like371 HER2 UC HER2 UC HER2 UC Basal-like UC Basal-like UC 371 Luminal A Basal-like UC Basal-like UC Luminal A UC Basal-like UC373 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 373 Luminal B Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A374 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 374 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B375 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 375 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2377 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 377 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like378 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 378 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B379 Luminal A UC Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 379 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B380 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 380 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A381 Luminal B UC Luminal B UC Luminal B UC Luminal B Luminal B Luminal B UC 381 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B383 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 383 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A385 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 385 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B387 Luminal A UC Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 387 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A388 Luminal B UC Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 388 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A389 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 389 Luminal B HER2 UC HER2 UC HER2 UC HER2 UC390 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 390 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A391 Luminal A UC Luminal A UC Luminal A UC Luminal A UC Luminal A UC 391 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A392 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 392 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2393 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 393 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B394 Luminal B UC Luminal B UC Luminal B UC Luminal B UC Luminal B UC 394 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B395 Luminal A UC Luminal A UC Luminal A UC Luminal A UC Luminal A UC 395 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A396 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 396 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2 HER2397 Luminal A UC Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 397 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A398 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 398 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like401 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 401 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B402 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 402 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like403 Luminal A UC Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 403 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B Luminal A Luminal A404 Luminal A UC Luminal A UC Luminal A Luminal A Luminal A Luminal A Luminal A UC 404 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A

SSP by Sorlie et al (Proc Natl Acad Sci USA 2003) SSP by Hu et al (BMC Genomics 2006)

Supplementary Table 3: Assignments of ‘NKI-295’ breast cancers8 using HUGO gene symbols, Ensembl gene identifiers or Unigene cluster identifiers for mapping of centroid/SSP gene lists and dataset, averaging of multiple probes identified to match a gene in a centroid/SSP list versus multiple probes representing one gene, and inclusion/ exclusion of cases with a correlation <0.1 to any centroid/SSP; and agreement with published molecular subtype classifications of ‘NKI-295’ breast cancers 11,12 according to the SSPs by Sorlie et al4 and Hu et al5.

ID: identifier; SSP: single sample predictor; UC: unclassified.

9

Sample ID SSP Sorlie et al 2003 SSP Sorlie et al 2003, cut-off <0.1

SSP Hu et al 2006 SSP Hu et al 2006, cut-off <0.1

SSP Parker et al 2009 SSP Parker et al 2009, cut-off <0.1

Sample ID Tumour diameter (mm)

Lymph node status

Histological grade

Age (years)

ER status PR status HER2 status IHC

HER2 status FISH

Sample ID ESR1 gene expression (probe average)

PGR gene expression (probe average)

ERBB2 gene expression (probe average)

GRB7 gene expression (probe average)

AURKA gene expression (probe average)

MKI67 gene expression (probe average)

B1 Luminal B UC Luminal A Luminal A Luminal A Luminal A B1 15 Negative 3 51 Positive Negative Negative Not amplified B1 9.76536 5.21461 5.53877 5.61290 8.28688 5.79114B11 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like B11 17 Negative 3 57 Negative Positive Negative Not amplified B11 5.21941 7.81473 5.47500 5.60111 9.64841 6.93801B12 Luminal B Luminal B HER2 UC Luminal B Luminal B B12 30 Positive 3 53 Negative Negative Positive Amplified B12 6.29366 5.34140 6.30287 7.20648 9.46187 7.15863B15 Luminal B Luminal B Luminal A UC Luminal B Luminal B B15 17 Positive 3 38 Positive Positive Negative Not amplified B15 10.14939 6.95380 5.13112 5.42255 8.20300 6.60413B16 Luminal B Luminal B Luminal A UC Luminal B Luminal B B16 25 Positive 3 57 Positive Positive Negative Not amplified B16 12.36096 6.85743 5.43389 5.33667 9.92846 6.87730B17 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like B17 23 Negative 3 53 Negative Negative Negative Not amplified B17 6.47691 5.40935 5.47067 5.29320 9.69089 6.66634B2 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like B2 25 Positive 3 48 Negative Negative Negative Not amplified B2 6.19215 5.23952 5.51443 5.89781 9.25762 7.44693

B20 Luminal B Luminal B Luminal A UC Luminal B Luminal B B20 18 Negative 3 45 Negative Negative Positive Amplified B20 9.23400 5.20420 6.03847 6.31728 8.76053 7.22596B21 Luminal B Luminal B Luminal A UC Luminal B Luminal B B21 40 Positive 3 61 Positive Positive Negative Not amplified B21 11.68897 5.72573 5.45259 5.42618 8.33442 6.13083B24 Luminal B Luminal B Luminal A UC Luminal B Luminal B B24 15 Negative 3 67 Positive Negative Negative Not amplified B24 11.61838 5.29903 5.37451 5.26115 9.37260 7.34784B26 Luminal B Luminal B Luminal A UC Luminal B Luminal B B26 20 Negative 3 37 Positive Negative Positive Amplified B26 10.19462 5.25800 6.62406 7.46103 9.15953 6.87391B27 Luminal A UC Luminal A Luminal A Luminal A Luminal A B27 27 Positive 3 43 Positive Positive Negative Not amplified B27 10.65330 6.85625 5.44129 5.43292 8.15884 6.16520B29 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like B29 28 Negative 3 48 Negative Negative Negative Not amplified B29 5.36603 5.19632 5.44313 5.63115 8.99464 7.08802B30 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B B30 18 Negative 3 44 Positive Positive Negative Not amplified B30 11.74016 8.09174 5.37982 5.13553 8.69981 6.75184B31 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B B31 17 Negative 3 53 Positive Positive Negative Not amplified B31 12.03112 8.13288 5.56228 5.73603 9.85947 6.84896B32 Luminal B Luminal B HER2 UC Luminal B Luminal B B32 18 Negative 3 49 Negative Negative Positive Amplified B32 6.96895 5.11576 6.57420 7.53213 9.22656 6.96182B33 Luminal B Luminal B Luminal A UC Luminal B Luminal B B33 20 Positive 3 55 Positive Positive Negative Not amplified B33 12.35047 6.43200 5.18303 5.29565 8.55169 6.30294B34 Luminal B Luminal B Basal-like UC Luminal B Luminal B B34 50 Positive 3 75 Negative Negative Positive Amplified B34 7.33470 5.21722 6.72975 8.58556 9.96526 6.41040B35 Luminal B Luminal B HER2 UC Luminal B Luminal B B35 30 ND 3 80 Negative Negative Positive Amplified B35 5.96701 5.21386 6.63738 8.47235 9.18225 6.57713B37 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B B37 25 Positive 3 75 Positive Positive Negative Not amplified B37 11.72839 6.72433 5.15998 5.39756 8.54027 6.76050B39 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B B39 35 Positive 3 54 Positive Positive Negative Not amplified B39 12.23520 6.65351 5.59072 5.58617 9.68936 7.09054B40 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B B40 37 Positive 3 72 Negative Positive Positive Amplified B40 10.52570 5.19899 6.07988 6.79272 7.78331 6.03839B41 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like B41 17 Negative 3 70 Negative Negative Negative Not amplified B41 5.54856 5.15782 5.35887 5.98315 9.46255 6.88252B43 Luminal B Luminal B HER2 UC Luminal B Luminal B B43 20 Positive 3 59 Negative Negative Positive Amplified B43 7.59197 5.06703 6.36917 7.30603 9.37581 5.97404B44 Luminal B UC Luminal A UC Luminal B Luminal B B44 25 Positive 3 43 Positive Positive Negative Not amplified B44 11.05295 6.40236 5.33796 5.68801 11.07405 7.33501B45 Luminal B UC Luminal A UC Luminal B Luminal B B45 38 Positive 3 52 Negative Negative Negative Not amplified B45 6.83222 4.99552 5.51718 5.17064 8.32727 6.03335B46 Luminal B Luminal B HER2 UC Luminal B Luminal B B46 22 Negative 3 49 Negative Negative Positive Amplified B46 6.08859 5.19320 5.91371 7.49862 9.02068 6.56671B47 Luminal B Luminal B Luminal A UC Luminal B Luminal B B47 17 Negative 3 65 Positive Negative Negative Not amplified B47 9.86218 6.65955 5.56750 5.25708 10.06111 6.83349B49 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B B49 20 Negative 3 59 Positive Positive Negative Not amplified B49 11.12133 5.23903 5.47731 5.99772 8.64779 6.18244B5 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B B5 80 Positive 3 81 Positive Positive Negative Not amplified B5 12.28304 8.06673 5.53690 5.52322 8.58258 5.67674B6 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like B6 35 Negative 3 69 Negative Negative Negative Not amplified B6 6.95656 5.08976 5.43720 5.49995 9.51091 7.72670

B60 Luminal B Luminal B Luminal A UC Luminal B Luminal B B60 15 Negative 3 63 Positive Positive Negative Not amplified B60 11.69966 7.50853 5.59721 5.42478 9.06422 5.95365B61 Luminal B Luminal B Luminal A UC Luminal B Luminal B B61 27 Positive 3 55 Positive Positive Negative Not amplified B61 11.25171 5.46410 5.27842 5.05392 9.94565 6.67851B62 Basal-like Basal-like Basal-like UC Basal-like Basal-like B62 35 Positive 3 50 Negative Negative Negative Not amplified B62 7.48733 5.23117 5.49010 5.50034 9.00720 7.12329B64 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like B64 21 Negative 3 53 Negative Negative Negative Not amplified B64 5.17499 5.13145 5.65592 5.55284 9.19965 7.69776B65 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like B65 12 Negative 3 46 Negative Negative Negative Not amplified B65 6.11989 5.15083 5.44475 5.60085 8.71807 6.62827B66 Luminal B Luminal B HER2 UC Luminal B Luminal B B66 30 Negative 3 37 Negative Negative Positive Amplified B66 6.09542 5.17081 6.66837 8.21370 9.55977 6.41680B67 Luminal B UC Luminal A UC Luminal B UC B67 22 Positive 3 53 Negative Negative Negative Not amplified B67 9.90315 5.53395 5.39995 5.18079 9.12947 6.17574B69 Luminal B Luminal B HER2 UC Luminal B Luminal B B69 22 Negative 3 59 Negative Negative Negative Not amplified B69 6.06038 5.18055 5.60425 5.66509 9.77026 6.97381B7 Luminal B Luminal B Luminal A UC Luminal B Luminal B B7 27 Positive 3 70 Positive Negative Negative Not amplified B7 11.63405 5.03185 5.90219 5.94280 9.72205 6.90636

B72 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B B72 24 Negative 3 64 Positive Positive Negative Not amplified B72 11.94402 7.52742 5.89520 5.43518 8.30252 6.12734B74 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B B74 28 Positive 3 41 Positive Negative Negative Not amplified B74 11.52831 5.42112 5.38836 5.52662 9.18055 6.98128B76 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B B76 25 Negative 3 68 Positive Positive Positive-2+ Amplified B76 12.56534 6.49042 5.77225 6.32623 9.29861 6.81281B77 Luminal B Luminal B Luminal A UC Luminal B Luminal B B77 70 Positive 3 49 Positive Positive Positive Amplified B77 9.96281 6.96623 6.12863 6.64084 9.08612 6.57405B78 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like B78 22 Negative 3 35 Negative Negative Negative Not amplified B78 5.74722 5.44702 5.57033 5.77457 8.98219 7.73907B79 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like B79 24 Positive 3 50 Negative Negative Negative Not amplified B79 7.56879 5.19050 5.34997 5.22563 9.71730 7.04315B80 Luminal B Luminal B HER2 UC Luminal B Luminal B B80 30 Negative 3 30 Negative Negative Positive Amplified B80 5.93616 4.97807 6.12584 7.22713 8.85984 6.63950B81 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like B81 20 Negative 3 30 Negative Negative Negative Not amplified B81 7.06927 4.97187 5.38941 5.57138 10.41707 6.70546B82 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A B82 12 Negative 3 67 Positive Positive Negative Not amplified B82 11.75572 6.49205 5.59722 5.60578 8.67668 5.81966B84 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B B84 15 Positive 3 67 Negative Negative Negative Not amplified B84 12.26118 5.12679 5.43665 5.39882 8.17791 6.24519B86 Luminal B Luminal B Luminal A UC Luminal A UC B86 14 Negative 3 38 Negative Negative Negative Not amplified B86 8.41270 5.38863 5.42997 5.39824 9.61675 6.27498B87 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like B87 27 Positive 3 61 Negative Negative Negative Not amplified B87 6.20904 4.89081 5.31265 5.43581 9.06903 6.95664B9 Luminal B Luminal B Luminal A UC Luminal B Luminal B B9 26 Positive 3 55 Positive Negative Negative Not amplified B9 11.44420 5.13947 5.47265 5.57931 8.51564 6.49415

Supplementary Table 4: Molecular subtype assignment of 53 grade III IDCs using the single sample predictors by Sorlie et al4, Hu et al5 and Parker et al6 using HUGO gene symbol for probe mapping and averaging of multiple probes identified to match a gene in a centroid/SSP; and ER, PR and HER2 status as determined by immunohistochemistry (IHC), HER2 gene status as determined by fluorescence in situ hybridisation (FISH), age, histological grade, tumour size, lymph node status, and microarray-based mRNA expression levels of ESR1 , PGR , ERBB2 , GRB7 , AURKA and MKI67 .

ER: oestrogen-receptor; ND: not determined; PR: progesterone receptor; SSP: single sample predictor; UC: unclassified.

10




Sample ID Tumour diameter (mm)

Lymph node status (number postive nodes)

ER status Histological grade

Age (years)

Sample ID ESR1 gene expression (probe average)






4 Luminal B Luminal B HER2 UC Luminal B Luminal B 4 20 0 Positive 3 41 4 -0.02170 2.15594 -2.30482 -2.02195 -0.20595 -0.089316 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 6 13 0 Positive 2 49 6 0.24450 0.30353 -1.53562 -1.62812 -0.81312 0.053897 Normal breast-like UC Normal breast-like Normal breast-like Normal breast-like Normal breast-like 7 20 0 Negative 1 46 7 -2.54718 0.38975 -1.31829 -1.56674 -1.67276 -0.112038 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 8 28 0 Negative 3 48 8 -2.72447 -1.69830 -2.60467 -2.20630 0.91481 0.245299 Luminal A UC Luminal A Luminal A HER2 UC 9 15 0 Positive 3 48 9 -0.59898 0.01272 -1.31318 -2.03470 -0.82061 -0.46332

11 Luminal B Luminal B HER2 HER2 HER2 HER2 11 22 0 Positive 3 37 11 -0.98239 -0.65150 0.93747 0.75127 0.21111 0.1917012 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 12 22 0 Negative 3 46 12 -5.28586 -2.50801 -2.41516 -1.83139 1.21177 -3.0859213 Luminal B UC Luminal B Luminal B HER2 HER2 13 21 0 Positive 3 41 13 -0.54304 -1.05579 0.79890 0.34420 0.47646 0.6573314 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 14 10 0 Positive 1 48 14 0.19610 -0.15844 -1.20580 -1.73994 -1.25502 -0.4201117 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 17 17 0 Positive 2 48 17 -0.11514 0.51093 -1.94934 -2.15195 -0.81146 -0.5953126 Luminal B UC Luminal A Luminal A Luminal A Luminal A 26 14 0 Positive 3 40 26 -0.44153 -1.16966 -2.80815 -3.00829 -0.86953 -0.2428927 Normal breast-like Normal breast-like Luminal A Luminal A Luminal A Luminal A 27 20 0 Positive 1 45 27 0.09477 2.32364 -1.70929 -2.25854 -1.04387 0.2411828 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like 28 15 0 Negative 3 40 28 -2.22097 1.03177 -1.87529 -2.17448 -1.64165 -0.0401929 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Luminal A Luminal A 29 12 0 Positive 2 52 29 0.34308 0.33234 -2.22658 -2.76165 -1.14236 0.2123736 Luminal A UC Luminal A Luminal A Luminal A Luminal A 36 10 0 Positive 2 52 36 0.50236 -1.44759 -2.77591 -3.11755 -0.37191 0.1181038 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B 38 14 0 Positive 2 52 38 0.78729 1.95627 -2.68779 -2.24672 -0.12319 -0.0191639 Luminal B UC Luminal A Luminal A Luminal A Luminal A 39 25 0 Positive 3 46 39 0.29249 0.43609 -2.40850 -1.64862 -0.39904 -0.2911345 Luminal A Luminal A Luminal B Luminal B Luminal A Luminal A 45 25 0 Positive 3 37 45 1.18591 -0.94951 -1.15187 -1.30794 -0.13198 -0.3490648 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 48 32 0 Negative 3 30 48 -4.17269 -2.04706 -2.64924 -2.45731 0.69443 0.0931651 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B 51 35 0 Positive 3 41 51 0.67649 0.61018 -2.35564 -2.24639 -0.73651 0.0233756 Normal breast-like UC Luminal A Luminal A Luminal B Luminal B 56 14 0 Positive 2 30 56 0.13340 -0.05378 -2.92151 -2.38926 -0.58112 -0.1834357 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 57 25 0 Negative 3 28 57 -5.08291 -3.42704 -3.60411 -2.94967 1.19516 0.5446558 Luminal B UC Luminal B Luminal B Luminal B Luminal B 58 30 0 Positive 3 38 58 -0.27369 1.81161 -1.85152 -1.94382 0.37427 0.9581659 Luminal B UC Luminal B Luminal B Luminal B Luminal B 59 30 0 Positive 3 44 59 0.41782 -1.55810 -2.54624 -2.94854 0.76935 -0.0115060 HER2 HER2 Luminal A Luminal A Luminal A Luminal A 60 16 0 Positive 3 45 60 -0.16549 -1.74144 2.36931 2.05690 -0.16601 -0.1560661 Luminal B Luminal B Luminal A Luminal A Luminal A Luminal A 61 9 0 Positive 3 38 61 -0.25610 -0.40648 -2.02592 -1.71224 -0.79034 -0.1635562 HER2 HER2 HER2 HER2 HER2 HER2 62 25 0 Positive 3 36 62 -0.67775 -2.36990 1.60004 1.79293 0.42351 0.1634571 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 71 30 0 Negative 3 48 71 -4.10405 -1.81122 -2.70768 -1.44281 0.72898 1.1012472 Luminal A UC Luminal A Luminal A Luminal B Luminal B 72 30 0 Positive 2 39 72 0.20684 -0.22730 -2.95944 -1.48999 0.05415 -0.2383273 Basal-like Basal-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like 73 27 0 Positive 3 50 73 -2.11049 -1.39234 -2.62335 -3.13296 -1.85464 -0.2962675 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 75 28 0 Negative 3 52 75 -3.50730 -1.41337 -2.88758 -2.35604 -0.13542 0.1561976 HER2 HER2 Basal-like Basal-like HER2 HER2 76 30 0 Negative 2 52 76 -3.53161 -2.10402 1.45483 1.85897 -0.03759 0.07801

103 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 103 30 0 Negative 3 42 103 -4.85767 -1.77743 -2.87371 -2.23602 0.48814 0.33194107 Luminal A Luminal A Luminal B Luminal B Luminal B Luminal B 107 2 0 Positive 3 38 107 0.46041 0.21472 -3.64154 -2.53330 0.63656 0.35055109 HER2 HER2 HER2 HER2 HER2 HER2 109 20 0 Negative 3 41 109 -3.94728 -2.14137 2.10496 2.46342 0.11776 0.03633110 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 110 35 0 Positive 3 51 110 1.10393 0.21113 -1.50184 -1.90344 1.45887 0.27625111 Luminal B Luminal B HER2 HER2 HER2 HER2 111 25 0 Positive 3 50 111 -1.29187 -0.76477 1.38489 2.16971 1.80990 0.65590113 HER2 UC Normal breast-like Normal breast-like HER2 HER2 113 12 0 Negative 2 47 113 -2.72825 -1.87808 -2.39084 -2.31141 -0.21525 -0.39162117 Luminal B UC Luminal A Luminal A Luminal B Luminal B 117 15 1 Positive 3 51 117 -0.45226 1.13383 -2.85376 -3.36116 -0.47516 -0.09936118 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 118 17 0 Positive 2 47 118 0.38184 1.17713 -2.17175 -1.88115 -0.41331 -0.12452120 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 120 13 0 Positive 2 42 120 1.33526 1.43756 -2.20665 -1.69763 -1.45008 -0.66813122 Luminal A UC Luminal A Luminal A Luminal A Luminal A 122 25 0 Positive 2 43 122 -1.37513 -0.72815 -0.79972 -1.24557 -1.36560 -0.21007123 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 123 20 0 Positive 3 48 123 0.64861 0.58658 -1.48764 -1.57280 -0.42405 -0.40324124 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 124 15 0 Positive 2 38 124 1.98046 0.96240 -1.58035 -2.35923 -0.27265 0.05825125 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 125 15 1 Positive 2 50 125 1.66524 0.84335 -1.11474 -1.41134 -1.29058 -0.01196126 Luminal A Luminal A Luminal B Luminal B Luminal B Luminal B 126 15 0 Positive 2 38 126 -0.22181 -0.04979 0.70541 0.35509 -0.16937 -0.05803127 Luminal A Luminal A Luminal B Luminal B Luminal B Luminal B 127 10 1 Positive 1 42 127 0.40481 -0.47026 -2.21175 -2.39192 0.19310 0.09784128 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B 128 25 1 Positive 1 50 128 0.90825 0.23676 -0.70508 -1.36120 -0.33276 0.30653129 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 129 15 3 Positive 2 43 129 0.29500 -0.02652 -1.85980 0.13010 -0.36701 -0.03731130 HER2 HER2 HER2 HER2 HER2 HER2 130 18 1 Negative 3 47 130 -3.34299 -1.41825 2.48759 2.69986 0.02996 2.15968131 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 131 17 0 Negative 3 39 131 -4.39882 -1.74442 -1.44923 -1.77088 0.53644 0.92382132 Luminal B UC Luminal A Luminal A Luminal B Luminal B 132 15 1 Positive 2 47 132 -0.67324 1.48510 -1.69289 -1.80416 2.07696 0.52043133 HER2 UC Luminal A Luminal A Luminal A Luminal A 133 18 0 Positive 1 32 133 -0.83745 0.37008 -0.96872 -0.77149 -0.95030 -0.21897134 HER2 UC Luminal A Luminal A Basal-like UC 134 12 1 Positive 3 38 134 -0.53931 0.81647 -1.45991 -2.00031 0.23928 0.12780135 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 135 20 2 Negative 3 45 135 -3.85564 -1.57892 -2.81850 -1.59420 1.48559 0.34852136 Luminal B Luminal B HER2 HER2 HER2 HER2 136 40 2 Negative 3 31 136 -2.19822 -0.80069 2.60235 3.79537 1.04258 -0.26775137 Luminal A UC Luminal A Luminal A Luminal A Luminal A 137 18 1 Positive 1 41 137 0.32800 -0.64470 -1.42639 -1.39737 -0.69298 0.00120138 HER2 HER2 Normal breast-like Normal breast-like Normal breast-like UC 138 15 0 Positive 3 44 138 -1.44761 -0.15447 -1.60757 -2.00061 -0.94887 0.02258139 Luminal B Luminal B Luminal A UC Normal breast-like Normal breast-like 139 45 0 Positive 3 41 139 -0.16005 -0.92725 -2.32041 -1.75836 0.15593 0.20368140 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 140 18 0 Positive 1 46 140 0.11488 -0.54797 -1.10845 -0.69165 -0.77589 -0.06835141 HER2 HER2 Basal-like Basal-like HER2 HER2 141 30 0 Negative 3 33 141 -4.17028 -1.38651 2.73034 2.74394 0.39186 0.11351142 Luminal B Luminal B Normal breast-like Normal breast-like Normal breast-like Normal breast-like 142 20 0 Positive 3 39 142 -1.28658 -0.26438 -1.21905 -1.87187 -0.85606 0.25768144 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 144 30 0 Negative 3 38 144 -3.61735 -2.53190 -3.82992 -2.24400 0.41391 -0.05752145 Luminal A Luminal A Luminal B Luminal B Luminal B Luminal B 145 19 2 Positive 2 48 145 -0.54690 0.54213 -1.16153 -1.31814 -0.63210 0.41214146 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B 146 30 4 Positive 3 47 146 0.02798 1.30860 -1.29783 -2.01647 -0.35127 -0.63564147 HER2 HER2 HER2 HER2 HER2 HER2 147 17 1 Negative 2 38 147 -4.33156 -2.09482 2.19124 2.03122 -0.33362 -0.00396148 Luminal A UC Luminal A Luminal A Luminal A Luminal A 148 50 0 Positive 3 49 148 1.93437 -1.55537 -0.81596 -0.99102 -0.50539 -0.21169149 HER2 HER2 HER2 HER2 HER2 HER2 149 30 3 Negative 2 44 149 -2.94250 -2.98926 2.34087 2.27061 -0.32246 -0.35903150 Luminal B Luminal B Luminal B Luminal B HER2 HER2 150 20 6 Positive 2 36 150 -1.40050 -1.66528 2.47775 2.18887 0.55966 0.15832151 Luminal B Luminal B Basal-like UC Luminal B Luminal B 151 40 4 Positive 3 42 151 -0.89167 0.58531 -1.43537 -2.05442 -0.33456 -0.19280153 HER2 HER2 HER2 UC HER2 HER2 153 50 0 Negative 3 37 153 -3.34799 -1.47347 -0.22463 -0.58628 -0.50026 0.06437154 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 154 15 0 Positive 1 40 154 1.33826 1.07629 -1.14213 -1.91108 -1.33752 -0.35341155 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 155 40 0 Positive 3 49 155 0.51035 -0.25679 -1.42934 -1.24922 -0.51047 0.05935156 Normal breast-like UC Luminal A Luminal A Luminal A Luminal A 156 21 4 Positive 3 42 156 0.28907 1.35091 -1.16387 -1.47683 -0.29696 -0.03477157 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 157 30 1 Positive 1 45 157 1.17102 2.56325 -0.95884 -1.88354 -0.66168 -0.20268158 HER2 HER2 HER2 HER2 HER2 HER2 158 28 1 Negative 3 49 158 -3.94894 -1.57611 2.88090 -1.87434 0.39111 0.47528159 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B 159 20 3 Positive 2 44 159 0.02245 -0.17367 -1.13505 -0.67351 0.13228 0.53894160 Normal breast-like Normal breast-like Luminal A Luminal A Normal breast-like Normal breast-like 160 40 4 Positive 1 32 160 0.03572 0.43583 -1.09651 -1.43828 -0.80059 -0.20996161 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 161 40 9 Positive 1 46 161 -0.48901 0.69909 -1.41913 -2.45951 -0.78258 -0.41590162 Luminal B Luminal B Basal-like Basal-like Luminal B Luminal B 162 30 3 Positive 3 50 162 -0.37152 0.40377 -3.19206 -2.46796 0.18011 0.37240163 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 163 15 7 Positive 3 38 163 1.14163 -2.57353 -1.59896 -1.45896 1.10802 0.27282164 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 164 30 0 Negative 3 50 164 -4.51548 -2.56146 -2.76320 -2.84500 1.68066 1.30119165 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 165 15 0 Positive 3 39 165 0.51333 -1.29848 -2.43091 -2.32464 1.86131 -0.11558166 Luminal B UC Luminal B Luminal B Luminal B Luminal B 166 35 3 Positive 3 43 166 1.25858 -2.23175 -2.09126 -1.35846 0.46372 0.21761167 Luminal A UC Luminal A Luminal A Luminal A Luminal A 167 15 0 Positive 1 44 167 0.88831 1.01199 -0.78595 -1.39122 -0.95398 -0.22955169 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B 169 25 1 Positive 2 40 169 1.28650 1.07654 -1.14093 -0.34321 0.17935 0.08357170 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 170 25 2 Positive 1 42 170 0.21261 0.71042 -2.19655 -2.47966 -1.69139 -0.54030172 Luminal B Luminal B HER2 UC HER2 HER2 172 30 2 Positive 3 46 172 -0.38549 -2.04691 -0.39983 0.67627 0.60994 -0.22047174 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 174 20 1 Positive 3 41 174 -0.45188 -0.08478 -1.91589 -2.99009 0.06399 0.67891175 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 175 15 0 Negative 2 48 175 -5.02161 -1.92321 -3.67996 -2.44887 1.13351 0.58175176 Luminal B Luminal B Luminal A Luminal A Luminal A Luminal A 176 50 3 Positive 2 46 176 -0.98026 0.41237 -1.30848 -0.96326 -0.97741 -0.33407177 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 177 25 1 Negative 3 48 177 -3.01998 -2.08974 -1.40190 -0.19725 0.51141 -0.45255178 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like 178 30 1 Positive 2 48 178 0.07486 0.27261 -1.19446 -0.44552 -1.16800 -0.29451179 HER2 HER2 Basal-like Basal-like HER2 HER2 179 30 0 Negative 3 40 179 -2.99762 -1.63059 -0.36108 -0.41137 0.24793 0.21834180 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 180 45 7 Positive 3 36 180 -0.89918 -0.69879 -1.36224 -1.19090 0.20731 0.19676181 Luminal B Luminal B HER2 HER2 HER2 HER2 181 20 0 Negative 3 35 181 -4.33544 -1.74069 1.57471 1.85086 0.11538 0.73852182 Normal breast-like UC Normal breast-like Normal breast-like Normal breast-like Normal breast-like 182 11 1 Positive 1 43 182 -0.22329 -0.52360 -1.86236 -1.86468 -1.23038 -0.32462183 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 183 22 0 Positive 1 42 183 1.45769 1.15698 -1.48975 -2.03962 -0.93731 0.24725184 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 184 23 1 Negative 3 44 184 -3.74248 -1.44191 -3.29229 -2.54684 0.74771 0.10009185 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B 185 20 0 Positive 2 42 185 1.02882 0.03684 -1.76722 -1.78046 -0.70473 -0.40981186 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 186 24 1 Negative 2 47 186 -3.70771 -1.57683 -3.52888 -2.20942 1.71612 0.70742187 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like 187 20 2 Positive 2 40 187 -1.93648 0.00394 1.00527 0.27774 -0.78162 -0.20136188 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 188 15 1 Positive 1 41 188 1.43706 0.18893 -0.94126 -0.94804 -0.74194 -0.20903189 HER2 HER2 Basal-like Basal-like HER2 HER2 189 25 0 Positive 2 39 189 -2.15402 -0.65816 -0.25589 0.53101 0.91704 -0.06408190 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 190 20 1 Positive 1 48 190 0.62781 -0.43987 -1.71855 -2.22846 -0.28087 -0.34017191 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 191 45 0 Positive 3 34 191 0.85209 0.80601 -1.62671 -2.31517 -0.96687 -0.12035192 Luminal A Luminal A Luminal B Luminal B Luminal B Luminal B 192 20 3 Positive 2 41 192 1.39374 -0.24473 -1.55879 -1.35205 1.24833 0.28966193 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 193 8 0 Positive 1 50 193 0.26695 -0.24061 -2.13084 -1.97455 -0.74163 -0.19572194 HER2 UC Normal breast-like Normal breast-like Normal breast-like Normal breast-like 194 12 3 Positive 2 45 194 -0.61154 -0.16302 -1.56340 -2.24491 -0.36486 -0.39361195 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 195 20 3 Negative 2 45 195 -3.84765 -1.00886 -2.24420 -1.87864 -0.08395 -0.04463196 Normal breast-like Normal breast-like Luminal A Luminal A Normal breast-like Normal breast-like 196 25 2 Positive 1 47 196 0.27222 -0.44575 -1.04168 -1.12139 -1.18042 -0.28820197 HER2 HER2 Normal breast-like Normal breast-like Basal-like Basal-like 197 10 2 Negative 1 37 197 -4.34345 -2.04972 -3.84167 -5.14054 -2.05905 -0.20585

Supplementary Table 5: Molecular subtype assignment of 295 breast cancers (‘NKI-295’) 8 using the single sample predictors by Sorlie et al4, Hu et al5 and Parker et al6 using HUGO gene symbol for probe mapping and averaging of multiple probes identified to match a gene in a centroid/SSP; and ER status, age, histological grade, tumour size, lymph node status, and microarray-based mRNA expression levels of ESR1 , PGR , ERBB2 , GRB7 , AURKA and MKI67 .

11

198 HER2 HER2 Luminal A UC Normal breast-like Normal breast-like 198 20 2 Positive 2 43 198 -0.99907 -0.71623 0.95165 0.71027 -0.75401 -0.47325199 HER2 HER2 HER2 HER2 Normal breast-like Normal breast-like 199 15 0 Positive 3 39 199 -1.98567 -0.23775 2.83951 2.08280 -0.22518 -0.07875200 Normal breast-like Normal breast-like Luminal A Luminal A Luminal A Luminal A 200 20 1 Positive 2 43 200 1.09909 0.76251 -1.46707 -1.30763 -0.68618 -0.10128201 Normal breast-like UC Luminal A Luminal A Luminal A Luminal A 201 25 0 Positive 3 33 201 0.86070 1.68945 -1.84352 -1.91371 -0.59457 -0.21121202 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 202 39 0 Negative 3 47 202 -3.20790 -1.29209 2.66244 4.16670 -0.64406 0.16858203 HER2 HER2 Luminal A Luminal A HER2 HER2 203 23 1 Positive 3 49 203 0.63319 0.16270 2.65049 2.45564 0.23631 0.50415205 Luminal B Luminal B Luminal A UC Luminal B Luminal B 205 15 0 Positive 3 50 205 0.69568 1.07995 -1.15266 -1.75272 -0.47062 0.42844207 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 207 35 0 Positive 1 44 207 1.57291 0.19357 -0.96593 -0.64868 -0.23796 -0.28806208 HER2 HER2 HER2 HER2 HER2 HER2 208 30 3 Positive 3 45 208 -0.49347 -0.17745 1.06879 1.26801 -0.45503 -0.09545209 Luminal B Luminal B Luminal B UC Luminal B Luminal B 209 25 5 Positive 1 41 209 -0.17255 -0.01771 -1.50421 -1.28228 -0.31158 -0.14526210 HER2 HER2 HER2 HER2 HER2 HER2 210 30 1 Positive 1 50 210 -0.26074 -0.35780 0.47483 0.88497 -0.03876 0.48569212 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 212 20 0 Negative 2 42 212 -3.65108 -1.68826 -3.06164 -2.06748 0.46436 0.96259213 Luminal B UC Luminal B Luminal B Luminal B Luminal B 213 15 1 Positive 3 49 213 -0.53909 0.23794 0.07339 -0.86693 0.79305 -0.14519214 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 214 20 0 Positive 1 41 214 1.05466 1.20856 -1.32163 -1.14544 -0.89485 0.01995215 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 215 27 0 Negative 3 49 215 -4.51591 -1.73694 -3.11098 -1.83378 1.22191 -0.00431217 Luminal B Luminal B HER2 HER2 HER2 HER2 217 25 8 Negative 3 43 217 -4.74731 -1.87872 2.50322 1.68340 2.04774 0.75225218 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 218 25 3 Positive 3 38 218 0.15325 -0.88351 -2.15793 -2.50790 0.74162 0.33030219 HER2 HER2 Luminal A Luminal A Luminal A Luminal A 219 15 0 Positive 1 46 219 -2.14845 -1.13408 -1.29119 -1.97312 -1.09373 -0.04282220 Luminal A UC Luminal A Luminal A Luminal A Luminal A 220 20 1 Positive 1 42 220 0.90073 0.88878 -0.56546 -0.31018 -0.71086 -0.24647221 HER2 HER2 Luminal A Luminal A Luminal A Luminal A 221 19 0 Positive 2 45 221 -1.20149 -0.14756 2.27111 1.95744 -1.04295 0.13552222 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 222 15 0 Negative 3 34 222 -3.81738 -1.82772 -2.78861 -1.69108 0.76585 0.55748224 Luminal A UC Luminal A Luminal A Luminal B UC 224 20 0 Positive 1 44 224 -0.34886 -0.60219 -1.03161 -0.98188 -0.66865 -1.11778226 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 226 10 0 Negative 3 49 226 -4.40082 -2.18339 -2.33228 -1.75158 1.31051 0.43885227 Normal breast-like UC Luminal A Luminal A Luminal B Luminal B 227 20 0 Positive 3 39 227 0.07290 0.78380 -1.45496 -1.24623 -0.02801 -0.18562228 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 228 35 0 Negative 3 39 228 -4.65276 -2.12497 -2.39029 -1.44972 1.16987 0.66702229 Luminal B Luminal B HER2 HER2 HER2 HER2 229 30 0 Positive 3 45 229 -1.13215 -0.39658 1.92791 1.37822 -0.54407 0.22560230 HER2 HER2 Basal-like Basal-like HER2 HER2 230 20 0 Negative 3 28 230 -4.27819 -2.03258 2.27633 2.08932 0.22960 0.20343231 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 231 30 0 Positive 2 43 231 1.46955 1.56696 -1.09952 -0.61870 -0.96551 -0.19663233 Luminal A UC Luminal A Luminal A Luminal A Luminal A 233 25 0 Positive 1 42 233 -1.45451 1.08282 -1.07026 -1.71618 -0.85918 -0.22644235 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 235 17 0 Positive 1 47 235 0.14359 -0.02415 -1.87918 -1.14813 -0.17316 -0.51934236 Luminal B Luminal B HER2 HER2 HER2 HER2 236 20 2 Negative 3 49 236 -2.22418 -3.01040 1.45572 1.67013 0.48195 -0.00519237 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 237 25 0 Negative 3 50 237 -2.96107 -1.57809 -3.94675 -2.42986 0.30795 0.39448238 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 238 26 0 Negative 3 42 238 -4.19555 -1.84694 -2.80514 -2.52385 0.91056 0.67771239 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 239 10 0 Positive 1 40 239 0.50346 1.28299 -2.05854 -2.02466 -0.73181 0.22224240 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 240 40 0 Positive 3 47 240 -0.23544 -0.50215 -2.92780 -2.34549 2.58339 1.13698241 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 241 25 0 Negative 3 41 241 -3.94002 -1.72028 -1.20214 0.05057 0.51299 -0.16792243 Normal breast-like UC Luminal A Luminal A Luminal A Luminal A 243 15 1 Positive 2 44 243 -0.14382 -0.42711 -1.50101 -1.51357 -1.11034 0.35440245 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 245 35 4 Positive 3 48 245 0.01882 -0.62152 -2.35035 -2.46548 0.65286 1.09484246 HER2 HER2 HER2 HER2 HER2 HER2 246 14 0 Negative 3 35 246 -4.11025 -2.81328 3.08246 2.53422 -0.47410 -0.72507247 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B 247 20 1 Positive 2 50 247 0.21609 2.19991 -1.48679 -1.59790 -0.19309 0.71257248 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 248 15 0 Negative 3 40 248 -3.49270 -1.33957 -2.17809 -1.75386 0.90787 0.26801249 HER2 HER2 HER2 HER2 HER2 HER2 249 12 2 Positive 2 44 249 -1.13436 0.20007 1.82403 1.45444 -0.55037 0.49624250 Normal breast-like UC Luminal A Luminal A Luminal A Luminal A 250 15 0 Positive 1 39 250 -0.14339 0.41388 -1.53143 -1.20974 -0.76360 0.15702251 HER2 HER2 HER2 HER2 HER2 HER2 251 16 0 Positive 3 49 251 -1.73829 0.06675 1.38442 2.21708 -0.08152 0.92621252 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 252 18 0 Positive 3 46 252 -0.06183 -0.39998 -2.06075 -1.69902 0.61698 0.52226254 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B 254 27 0 Positive 3 37 254 -0.31745 0.09228 -1.12150 -1.57469 0.05264 -0.04171256 Normal breast-like UC Normal breast-like UC Normal breast-like Normal breast-like 256 40 4 Positive 1 49 256 -1.54050 -2.48088 -1.69693 -1.14190 -0.77530 -1.84947257 HER2 HER2 HER2 HER2 HER2 HER2 257 25 5 Negative 3 32 257 -3.28004 -2.06881 2.06494 2.44011 -0.35808 0.25679258 HER2 HER2 Normal breast-like UC HER2 HER2 258 20 1 Positive 2 43 258 -1.41089 -0.14362 2.22367 1.87873 -0.22255 0.88247259 Normal breast-like Normal breast-like Normal breast-like Normal breast-like HER2 HER2 259 13 0 Positive 1 42 259 -1.24084 -2.00365 0.78187 -0.05504 0.01704 0.94316260 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like Normal breast-like 260 18 2 Positive 2 42 260 0.27054 -0.33006 -0.92962 -0.60149 -0.37285 0.42734261 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 261 7 1 Positive 1 50 261 1.44594 0.16516 -0.43445 -0.25927 -1.63568 -0.10406263 Luminal B UC Luminal A UC Luminal B Luminal B 263 29 3 Positive 3 39 263 -0.56712 0.03347 -2.20548 -2.15139 1.05373 0.10464264 Luminal A UC Luminal A Luminal A Luminal B Luminal B 264 21 4 Positive 2 42 264 -0.09503 0.24278 -1.96971 -2.37952 -0.20828 -0.41819265 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 265 45 4 Negative 3 41 265 -4.30392 -1.85565 -1.55637 -1.10975 1.05472 0.00844266 Luminal B Luminal B Luminal B Luminal B HER2 HER2 266 11 0 Positive 1 43 266 -0.70890 -0.18942 2.11246 2.02209 0.03325 0.54657267 Luminal B Luminal B HER2 HER2 HER2 HER2 267 25 1 Positive 3 49 267 -1.02866 -0.70286 0.99808 0.78566 0.43616 0.08692268 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 268 35 0 Negative 3 38 268 -4.01307 -1.37836 -3.04436 -2.28519 0.72906 -0.02790269 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 269 35 7 Negative 3 38 269 -4.60391 -1.44451 -2.95508 -1.57657 0.71733 0.72480270 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 270 34 0 Negative 3 50 270 -4.56211 -1.93589 -3.30465 -1.36410 1.23986 0.12124271 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 271 10 0 Positive 1 42 271 0.95084 2.37098 -1.31620 -1.70669 -1.23935 -0.01586272 Luminal A UC Luminal A Luminal A Luminal B Luminal B 272 18 5 Positive 3 43 272 -0.13476 -0.45421 -2.15062 -2.84287 0.09122 0.21954273 HER2 HER2 Luminal B Luminal B Luminal B Luminal B 273 20 1 Positive 2 50 273 1.12373 -1.73916 2.17436 1.88869 0.17175 0.52414274 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 274 13 0 Positive 1 49 274 1.11315 -0.96242 -1.35423 -1.98453 -1.05441 -0.29163275 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B 275 50 6 Positive 2 49 275 0.87517 0.45928 -1.82055 -2.39289 -0.17497 -0.20056276 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 276 35 6 Negative 3 37 276 -4.34444 -1.24030 -2.76679 -2.84944 0.46524 0.22184277 Luminal A UC Luminal A Luminal A Luminal A Luminal A 277 12 1 Positive 1 37 277 -0.48522 1.48963 -2.78162 -2.99240 -1.03057 -0.27564278 Normal breast-like UC Luminal A Luminal A Luminal A Luminal A 278 35 0 Positive 2 49 278 -0.04697 -0.37401 -1.63639 -1.65119 -0.97212 -0.40334280 Normal breast-like UC Luminal A Luminal A Luminal A Luminal A 280 9 1 Positive 1 48 280 0.38279 -0.25070 -1.12336 -1.60252 -1.21511 -0.42184281 Normal breast-like Normal breast-like Luminal A Luminal A Luminal A Luminal A 281 20 1 Positive 2 48 281 -0.35059 1.02774 -0.88409 -1.51377 -0.55182 0.02613282 Normal breast-like UC Luminal A Luminal A Luminal A Luminal A 282 18 2 Positive 1 48 282 0.91255 2.13654 -1.30291 -1.33058 -1.02412 -0.39381283 Luminal A UC Luminal A Luminal A Luminal B Luminal B 283 22 4 Positive 3 49 283 0.65495 1.14132 -2.80101 -2.38504 -0.33536 -0.06890284 Luminal A UC Luminal B Luminal B Luminal B Luminal B 284 40 8 Positive 2 45 284 0.17092 -0.20602 -2.28016 -1.97206 0.27384 -0.27035285 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 285 25 0 Positive 2 43 285 1.72302 1.29077 -1.99787 -2.18822 -0.91043 -0.02889286 HER2 HER2 HER2 HER2 HER2 HER2 286 15 0 Positive 2 41 286 -0.63235 -1.18368 2.14627 2.24396 -0.03277 0.22660287 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 287 42 3 Positive 2 44 287 1.35195 0.59847 -0.84510 -0.54820 -1.37341 -0.47363288 HER2 HER2 HER2 HER2 HER2 HER2 288 25 1 Positive 3 35 288 -1.96018 0.29734 1.88364 0.99619 0.47779 -0.27653290 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 290 15 2 Positive 1 49 290 1.28265 1.89205 -1.11797 -0.63954 -0.83684 -0.44512291 Normal breast-like UC Basal-like UC Luminal B Luminal B 291 12 2 Positive 2 39 291 -1.38538 -0.78653 -1.86022 -1.58643 0.58508 -0.29046292 Luminal B UC Luminal A Luminal A Luminal A Luminal A 292 10 0 Positive 1 48 292 0.18149 -1.09269 -1.02408 -1.69016 -0.80405 -0.32905293 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B 293 18 1 Positive 1 46 293 1.11314 1.20742 -2.78567 -2.23265 -0.51414 -0.30540294 Luminal B UC Luminal B Luminal B Luminal B Luminal B 294 35 9 Positive 2 49 294 -0.85035 -0.13092 -1.12875 -2.17686 0.45131 0.68418295 Luminal B UC Luminal A Luminal A Luminal A Luminal A 295 21 0 Positive 1 48 295 -0.43617 0.31396 -0.98614 -0.95809 -0.68519 -0.11531296 Luminal B Luminal B Luminal B Luminal B HER2 HER2 296 23 0 Positive 3 46 296 -1.33139 -0.37013 1.07077 1.81370 1.92482 0.42939297 Luminal A UC Luminal B Luminal B Normal breast-like Normal breast-like 297 30 5 Positive 2 37 297 -0.36841 -1.21241 -1.12814 -1.03237 -0.27560 -0.05716298 Luminal A UC Luminal A Luminal A Luminal A Luminal A 298 35 1 Positive 1 50 298 0.28841 -0.40064 -1.46177 -1.40263 -0.58768 -0.50226300 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B 300 13 5 Positive 2 35 300 -0.61620 -0.73968 -0.51312 -1.37515 -0.40131 0.66879301 Luminal A UC Luminal A Luminal A Luminal B Luminal B 301 20 3 Positive 1 47 301 0.10373 -0.21236 -3.04549 -3.02842 -0.75601 -0.43754302 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B 302 24 0 Positive 3 47 302 1.92777 -0.30504 -2.21056 -1.25783 0.35729 0.16069303 Luminal A UC Luminal A Luminal A Luminal A Luminal A 303 25 3 Positive 2 43 303 -0.77943 -0.58601 -1.82085 -2.47776 -0.94109 -0.29698304 HER2 UC Normal breast-like Normal breast-like Luminal A Luminal A 304 15 0 Positive 1 40 304 0.40474 -1.36898 -1.23962 -1.53649 -0.89478 -0.48520305 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 305 30 0 Positive 1 40 305 0.09273 0.67070 -1.93529 -2.11490 -0.31796 0.08995306 Luminal B UC Luminal A Luminal A HER2 HER2 306 20 0 Positive 2 43 306 -0.29838 1.55048 -1.49930 -1.65498 -0.45216 0.94305307 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 307 30 9 Negative 3 44 307 -4.37079 -1.64773 -0.83623 -0.16406 1.21119 0.30845308 HER2 HER2 HER2 HER2 HER2 HER2 308 20 2 Positive 2 41 308 -1.93051 -0.66375 2.02576 2.17621 0.07807 0.05486309 Luminal B UC Luminal A Luminal A Luminal A Luminal A 309 22 4 Positive 2 43 309 0.53424 1.09823 -2.07293 -1.80113 -0.95457 -0.37186310 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 310 15 3 Negative 3 45 310 -4.57940 -2.08586 -2.13096 -0.30167 0.21890 0.33563311 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 311 35 4 Positive 2 42 311 0.36327 -1.00624 -2.08342 -2.14158 0.25642 0.08751312 Luminal B Luminal B Luminal A UC Luminal B Luminal B 312 28 0 Positive 2 47 312 -0.15141 -0.17229 -2.15956 -2.22580 -0.09052 0.07305313 Luminal B UC Luminal A Luminal A Luminal A Luminal A 313 17 0 Positive 2 40 313 -1.27954 0.54753 -1.41028 -1.48776 -0.55417 0.03909314 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 314 20 2 Positive 2 39 314 0.23427 -1.45352 -1.20562 -1.24760 0.78124 -0.17656315 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 315 15 1 Positive 1 40 315 0.37407 -1.07593 -1.25616 -1.57976 -1.46949 -0.79414317 Luminal B UC Luminal B Luminal B Luminal B Luminal B 317 15 0 Positive 2 43 317 0.82346 -2.65697 -1.65047 -0.98492 -0.05257 -0.37836318 Luminal A Luminal A Luminal A Luminal A Normal breast-like Normal breast-like 318 15 2 Positive 1 37 318 -0.02063 -0.81062 -0.65919 -0.82896 0.30270 -0.31762319 Luminal B Luminal B HER2 HER2 HER2 HER2 319 30 0 Positive 3 48 319 -1.64265 0.83111 1.15031 1.43129 -0.31296 -0.59992320 Luminal B Luminal B Basal-like Basal-like Luminal B Luminal B 320 15 1 Positive 3 44 320 -0.75919 0.10626 -2.24824 -1.43886 0.22964 -0.95958321 HER2 HER2 Luminal A Luminal A HER2 HER2 321 30 9 Positive 2 39 321 -1.25847 -0.94535 -1.60019 -1.66583 -0.80751 -0.36863322 Luminal A UC Luminal B Luminal B Luminal B Luminal B 322 25 2 Positive 2 45 322 0.59191 -1.55445 -2.47047 -1.73197 1.47525 1.47377323 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 323 25 0 Positive 1 41 323 0.75207 0.89178 -1.37017 -1.52059 -2.46668 -0.77376324 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 324 40 2 Negative 3 46 324 -3.48011 -1.65237 -1.54947 -0.95546 0.46667 0.73619325 Luminal B UC Luminal A Luminal A HER2 HER2 325 18 8 Positive 1 42 325 -0.87425 -2.37323 -1.43816 -1.73776 -1.12235 -1.39736326 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 326 28 0 Negative 3 39 326 -3.90836 -2.25167 -2.45490 -1.47931 1.15194 0.61073327 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 327 20 2 Positive 2 49 327 0.11167 2.05358 -2.34348 -2.02028 0.46165 0.24320328 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 328 18 1 Positive 1 41 328 1.20331 1.19857 -1.41769 -0.67663 -1.64326 -0.71549329 Luminal B UC Luminal B Luminal B Luminal B Luminal B 329 22 0 Positive 1 49 329 0.20519 1.95778 -0.92743 -0.82628 -0.10483 0.22630330 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 330 15 13 Negative 3 26 330 -3.33242 -2.27818 -2.62702 -1.97922 0.35263 0.21402331 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 331 17 0 Positive 1 48 331 0.76047 -0.49206 -1.25113 -1.36732 0.47071 1.06816332 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 332 21 1 Negative 3 49 332 -4.87153 -2.89340 -3.10126 -1.36889 -0.32794 0.81667

12

333 HER2 HER2 HER2 HER2 HER2 HER2 333 21 0 Negative 3 44 333 -4.69579 -2.84605 1.48603 1.68676 0.22448 -0.82757334 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 334 22 1 Positive 2 36 334 0.27654 -0.11867 -1.57072 -1.68146 -1.66889 0.29746335 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 335 42 1 Negative 3 48 335 -3.75158 -1.84462 -2.62818 -2.13318 0.43137 -0.41182336 Luminal B UC Luminal A Luminal A Luminal A Luminal A 336 7 0 Positive 1 47 336 -0.32004 0.99928 -1.24814 -1.76767 -1.29251 -0.89892337 Luminal A UC Luminal B Luminal B Luminal B Luminal B 337 18 2 Positive 1 29 337 -0.32917 -0.07387 0.41569 -0.09823 0.10630 -0.09517338 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 338 18 0 Negative 3 49 338 -4.62667 -1.40634 -2.49873 -1.93503 0.14068 -0.07700339 Luminal A Luminal A Luminal B Luminal B Luminal B Luminal B 339 20 0 Positive 2 45 339 1.73620 -0.42921 -1.67410 -1.91341 0.51005 -0.26174340 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 340 22 1 Positive 2 43 340 1.41448 0.48147 -2.83081 -2.71323 1.02488 0.48720341 HER2 HER2 HER2 HER2 HER2 HER2 341 30 4 Negative 2 45 341 -3.42333 -2.28057 2.10111 2.77138 0.24154 -0.14131342 Luminal A Luminal A Luminal B Luminal B Luminal B Luminal B 342 20 0 Positive 2 45 342 0.58171 1.48213 -1.79023 -1.42734 -0.07722 -0.38599343 Luminal A UC Luminal A Luminal A Luminal A Luminal A 343 15 1 Positive 1 45 343 0.70725 0.77918 -0.99451 -1.76731 -0.68015 -0.12493344 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 344 13 0 Negative 1 44 344 -4.14560 -2.23988 -3.09299 -2.38280 -0.04098 -0.39452345 Luminal A UC Luminal A Luminal A Luminal A Luminal A 345 25 4 Positive 2 47 345 0.20548 -1.47715 -1.80105 -2.39719 -1.18109 -0.49492346 Normal breast-like UC Luminal A Luminal A Normal breast-like Normal breast-like 346 28 1 Positive 2 49 346 0.37431 0.54535 -0.50418 -0.32573 -0.33447 -0.27025347 Basal-like UC Luminal A UC Basal-like Basal-like 347 17 11 Positive 1 41 347 -1.69878 -0.01504 -2.37634 -2.53749 -0.69904 -0.26522348 Luminal A UC Luminal A Luminal A Luminal A Luminal A 348 17 0 Positive 2 50 348 1.24666 0.19627 -0.93570 -0.46170 -0.07787 0.24847349 Luminal B UC Luminal A Luminal A Luminal B Luminal B 349 37 0 Positive 2 45 349 1.42817 0.95982 -1.17438 -0.90118 -0.29677 0.43600350 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 350 15 3 Negative 1 46 350 -3.94805 -1.91004 -3.43276 -2.77576 -0.24866 -0.23978351 Luminal B Luminal B HER2 HER2 HER2 HER2 351 14 2 Positive 3 41 351 -0.73299 0.50032 1.30393 1.53010 1.03474 0.53647352 Luminal A Luminal A Luminal A Luminal A Normal breast-like Normal breast-like 352 22 0 Positive 2 43 352 -0.55592 -0.09050 -1.32684 -1.92755 0.67415 -0.17276353 Luminal B UC Luminal A Luminal A Luminal B Luminal B 353 14 3 Positive 2 36 353 0.59411 -0.74219 -2.19232 -1.70548 -0.11983 -0.12134354 Luminal A UC Luminal A Luminal A Luminal B Luminal B 354 32 0 Positive 3 47 354 -0.28212 -0.31907 -1.82068 -1.81160 -0.02933 0.04838355 Luminal B UC Normal breast-like Normal breast-like Normal breast-like Normal breast-like 355 14 0 Positive 2 50 355 -0.17327 -0.98948 -0.69360 -2.05751 -0.66397 0.58066356 HER2 UC Luminal A Luminal A Luminal A Luminal A 356 16 0 Positive 1 49 356 -0.15812 -0.02837 -1.61803 -2.92001 -1.19634 -0.12534357 Normal breast-like Normal breast-like Luminal A Luminal A Luminal A Luminal A 357 12 2 Positive 1 38 357 1.12667 -0.00894 -0.89933 -1.28496 -1.38581 -0.42680358 Luminal A Luminal A Luminal A Luminal A Normal breast-like Normal breast-like 358 7 0 Positive 1 45 358 0.75241 -0.59121 -0.86017 -1.50255 -1.11672 -0.47699359 Luminal B UC Normal breast-like Normal breast-like Normal breast-like Normal breast-like 359 20 1 Positive 2 49 359 -0.34197 0.39442 -1.83911 -2.02502 -0.64706 0.02426360 Normal breast-like Normal breast-like Luminal A Luminal A Normal breast-like Normal breast-like 360 35 3 Positive 1 49 360 1.25114 -0.29140 -1.44437 -1.84801 -1.19471 0.55130361 Normal breast-like Normal breast-like Luminal A Luminal A Luminal A Luminal A 361 18 1 Positive 1 42 361 0.99964 1.16936 -1.82217 -1.69525 -1.56617 -0.54489362 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 362 25 5 Positive 3 46 362 -1.92502 -0.06597 -1.02790 -1.67992 1.06982 -0.41493363 Luminal A Luminal A Luminal B Luminal B Luminal B Luminal B 363 37 5 Positive 2 42 363 1.16837 -0.50231 -0.66976 -1.82267 0.61556 -0.38227364 HER2 HER2 HER2 UC HER2 HER2 364 19 0 Negative 2 49 364 -2.88310 -0.50367 2.73575 1.86873 0.71297 0.68543365 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 365 18 0 Positive 2 51 365 0.54330 1.21128 -1.73671 -2.54264 -0.06920 -0.23642366 Luminal B Luminal B Luminal A Luminal A Luminal A Luminal A 366 15 0 Positive 2 50 366 0.62148 -1.22272 -2.14767 -1.96850 -0.13363 -0.10011367 HER2 HER2 Basal-like Basal-like HER2 HER2 367 30 0 Positive 2 49 367 -1.71782 -0.60238 2.94410 1.65912 0.34081 -0.18607368 Luminal B UC Normal breast-like Normal breast-like Luminal A Luminal A 368 30 0 Positive 2 33 368 -0.55956 0.19531 -1.37749 -1.82156 0.13472 0.04980369 HER2 HER2 HER2 HER2 HER2 HER2 369 20 0 Negative 2 39 369 -4.43219 -2.42749 2.35510 2.32390 0.27359 0.15521370 Normal breast-like Normal breast-like Normal breast-like Normal breast-like Luminal A Luminal A 370 18 2 Positive 1 51 370 1.42426 -0.15037 -1.67442 -2.00115 -1.02603 -0.34956371 HER2 UC Basal-like UC HER2 HER2 371 20 0 Positive 2 51 371 -1.13472 -2.44513 -1.39471 -1.02284 -0.28662 0.75179373 Luminal B Luminal B Luminal A Luminal A Luminal A Luminal A 373 23 1 Positive 2 51 373 -1.13937 -2.14369 -0.33675 -0.90849 -1.19000 -0.84884374 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 374 15 1 Positive 1 52 374 0.77085 -1.64871 -1.40401 -1.69643 0.79611 0.20870375 HER2 HER2 HER2 HER2 HER2 HER2 375 30 1 Positive 3 52 375 -0.97869 -0.88069 1.24526 0.82968 -0.18767 -0.32501377 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 377 20 6 Negative 3 52 377 -4.01779 -1.54358 -2.25004 -2.28051 -0.03192 0.31057378 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 378 30 1 Positive 3 52 378 -1.14041 -1.87713 -2.64780 -2.89473 0.39137 0.15598379 Luminal A Luminal A Luminal B Luminal B Luminal B Luminal B 379 30 0 Positive 1 52 379 1.17073 -1.75228 -0.93118 -1.26928 1.68687 -0.29243380 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B 380 15 0 Positive 2 52 380 0.54521 0.73649 -1.96148 -1.51142 -0.06375 -0.15617381 Luminal B UC Luminal B Luminal B Luminal B Luminal B 381 30 1 Positive 2 52 381 -0.12505 -1.79919 -2.36330 -2.32910 0.09262 0.46392383 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 383 15 1 Positive 2 52 383 -0.12005 1.25649 -1.87608 -1.93553 0.06543 -0.07958385 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 385 30 1 Positive 3 53 385 1.31539 -1.67202 -1.88330 -2.24727 0.64195 0.13371387 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B 387 20 1 Positive 2 52 387 0.16632 0.41695 -2.26777 -3.04869 -0.77373 -0.58694388 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 388 15 0 Positive 2 52 388 0.68828 -0.65431 -1.25446 -2.05786 -0.35720 0.40936389 Luminal B Luminal B HER2 UC HER2 HER2 389 25 4 Positive 3 51 389 -0.97742 -1.28995 -2.41272 -2.10278 0.14176 0.16140390 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 390 7 1 Positive 1 51 390 0.74025 0.14762 -1.55421 -1.70790 -1.06798 -0.35753391 Luminal A UC Luminal A Luminal A Luminal A Luminal A 391 27 0 Positive 2 51 391 0.40902 -0.53513 -0.85585 -0.96989 -1.13846 -0.31001392 HER2 HER2 HER2 HER2 HER2 HER2 392 13 1 Positive 2 51 392 -0.91173 0.97088 2.39554 3.41426 0.24957 -0.09011393 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B 393 17 2 Positive 1 51 393 0.46504 -1.47081 -1.12475 -1.10766 0.23244 -0.48112394 Luminal B UC Luminal B Luminal B Luminal A Luminal A 394 17 0 Positive 2 51 394 1.66629 -0.58197 -0.83944 -1.24420 0.31733 -0.09551395 Luminal A UC Luminal A Luminal A Luminal A UC 395 25 11 Positive 2 51 395 -0.27766 0.02289 -0.84504 -1.67729 -0.69602 0.14476396 Luminal B Luminal B HER2 HER2 HER2 HER2 396 25 2 Negative 3 51 396 -4.09735 -1.84223 2.22058 2.71623 0.24502 -0.47960397 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B 397 27 0 Positive 2 51 397 1.95324 -0.69100 -1.91336 -2.09898 -0.94944 -0.41697398 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 398 25 0 Negative 3 34 398 -3.06054 -1.37766 -0.89243 -0.58691 0.63131 0.44892401 Luminal A Luminal A Luminal B Luminal B Luminal B Luminal B 401 22 0 Positive 2 41 401 1.39681 0.04073 -0.75299 -1.65955 -0.55598 -0.76429402 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like 402 15 0 Negative 1 47 402 -3.16552 -0.75227 -2.94618 -2.39909 0.49493 0.59102403 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A 403 30 3 Positive 1 47 403 -1.10148 -0.68035 -0.42294 -1.27036 -0.73781 -0.87404404 Luminal A UC Luminal A Luminal A Normal breast-like Normal breast-like 404 17 3 Positive 1 39 404 0.47306 -0.24687 -2.28473 -1.51306 -1.23323 -0.09493

ER: oestrogen-receptor; SSP: single sample predictor; UC: unclassified.

13

Sample ID SSP Sorlie et al 2003 SSP Sorlie et al 2003, cut-off <0.1 SSP Hu et al 2006 SSP Hu et al 2006, cut-

off <0.1 SSP Parker et al 2009 SSP Parker et al 2009, cut-off <0.1 Sample ID Lymph node

status ER status Sample ID ESR1 gene expression (probe average)






GSM36777 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM36777 Negative Positive GSM36777 4.62179 5.30380 5.85645 6.25210 6.27288 5.32382GSM36778 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B GSM36778 Negative Positive GSM36778 5.10534 2.63906 5.72980 5.90454 7.29526 6.30727GSM36779 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36779 Negative Positive GSM36779 5.31541 5.01396 5.19825 5.56145 5.19850 5.07652GSM36780 HER2 HER2 HER2 HER2 HER2 HER2 GSM36780 Negative Negative GSM36780 4.32727 3.06805 7.75703 8.70170 6.13405 6.06843GSM36781 Luminal B Luminal B HER2 HER2 HER2 HER2 GSM36781 Negative Positive GSM36781 4.37093 2.07944 7.37984 6.97129 6.54103 6.30227GSM36782 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM36782 Negative Positive GSM36782 4.77342 5.08140 5.65385 6.08199 6.08199 5.34604GSM36783 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM36783 Negative Positive GSM36783 4.96823 6.44857 5.74909 6.15252 5.65249 5.38029GSM36784 Luminal B UC Luminal A Luminal A Luminal A Luminal A GSM36784 Negative Positive GSM36784 5.04392 3.20275 6.41799 6.20859 5.96358 5.96864GSM36785 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36785 Negative Positive GSM36785 6.12952 2.02815 5.48404 5.95920 6.00042 5.99242GSM36786 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM36786 Negative Positive GSM36786 4.75283 5.16307 6.49358 6.33629 6.14096 5.22336GSM36787 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36787 Negative Positive GSM36787 5.68324 5.35753 5.49855 5.92986 6.80239 5.90652GSM36788 Luminal B Luminal B Basal-like Basal-like Basal-like Basal-like GSM36788 Negative Negative GSM36788 4.11743 2.29253 4.55318 5.58048 7.07081 6.46715GSM36789 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36789 Negative Positive GSM36789 5.05973 3.85015 5.99200 5.37064 7.12866 6.03713GSM36790 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM36790 Negative Positive GSM36790 4.97042 5.46426 5.43203 5.32496 5.49183 4.44918GSM36791 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM36791 Negative Negative GSM36791 5.30266 5.27146 5.74361 6.24940 6.32597 5.82781GSM36792 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36792 Negative Positive GSM36792 4.97082 4.67749 5.19651 5.89026 6.27118 5.88547GSM36793 Basal-like UC Normal breast-like UC Normal breast-like Normal breast-like GSM36793 Negative Negative GSM36793 4.44804 2.76001 5.56790 6.15486 6.03381 5.80421GSM36794 Luminal B Luminal B HER2 UC Luminal B Luminal B GSM36794 Negative Positive GSM36794 4.88670 4.24850 6.03237 5.53339 5.86477 5.62864GSM36795 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36795 Negative Negative GSM36795 4.50971 2.93916 5.78566 6.81465 6.31951 6.31617GSM36796 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM36796 Negative Positive GSM36796 5.02515 5.98066 5.14550 6.24843 6.23539 5.79359GSM36797 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36797 Negative Negative GSM36797 4.14048 2.06686 5.54660 5.80544 7.18834 6.50059GSM36798 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36798 Negative Negative GSM36798 4.65166 2.77259 4.63397 5.63193 6.41706 6.28109GSM36799 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM36799 Negative Positive GSM36799 4.76065 2.29253 6.99383 7.08573 6.07304 5.87787GSM36800 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36800 Negative Negative GSM36800 5.69511 6.20980 6.55984 6.21120 5.88221 5.72085GSM36801 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM36801 Negative Positive GSM36801 5.38590 2.20827 5.62704 6.56695 6.50683 5.70545GSM36802 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36802 Negative Positive GSM36802 4.81244 6.26891 5.07592 5.99993 6.02151 5.00185GSM36803 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36803 Negative Positive GSM36803 5.56204 4.52937 5.23515 5.74876 6.13231 5.67078GSM36804 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM36804 Negative Positive GSM36804 4.80049 5.93436 5.79815 5.99770 5.77734 5.43118GSM36805 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM36805 Negative Positive GSM36805 5.42605 6.16395 5.74725 6.45457 5.70744 5.75961GSM36806 Luminal B Luminal B Luminal A Luminal A Luminal A Luminal A GSM36806 Negative Positive GSM36806 4.39521 6.12030 5.89157 6.47204 5.65704 5.36759GSM36807 Luminal A UC Luminal A Luminal A Normal breast-like Normal breast-like GSM36807 Negative Positive GSM36807 5.00366 5.58800 6.05985 6.15910 6.00734 5.41971GSM36808 Luminal B UC HER2 UC Basal-like UC GSM36808 Negative Negative GSM36808 5.16031 2.89037 6.07957 5.75732 6.34844 5.90479GSM36809 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36809 Negative Negative GSM36809 4.13149 2.09186 5.06954 5.57671 7.06373 6.16749GSM36810 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36810 Negative Positive GSM36810 4.81350 5.77393 6.33843 6.20879 5.99943 6.03459GSM36811 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM36811 Negative Positive GSM36811 5.06715 5.69002 5.82377 5.04471 6.40770 5.77907GSM36812 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36812 Negative Negative GSM36812 4.52144 5.55683 4.54067 4.57883 5.51020 5.25680GSM36813 Luminal B Luminal B Luminal A UC Luminal B Luminal B GSM36813 Negative Positive GSM36813 5.95989 3.72328 5.74216 5.75226 6.31173 6.15088GSM36814 Luminal B Luminal B HER2 UC HER2 HER2 GSM36814 Negative Positive GSM36814 4.70675 5.54322 6.88938 6.18022 6.32472 5.84296GSM36815 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36815 Negative Positive GSM36815 4.91918 2.79728 6.25645 5.82305 5.60801 5.43467GSM36816 Luminal B Luminal B HER2 UC Basal-like Basal-like GSM36816 Negative Negative GSM36816 4.63536 5.09742 4.82428 5.43938 6.57018 5.90005GSM36817 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36817 Negative Positive GSM36817 4.61242 4.86753 4.81581 5.33465 5.93938 6.02430GSM36818 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM36818 Negative Positive GSM36818 5.37278 5.72489 5.74674 5.86618 5.99446 5.68248GSM36819 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM36819 Negative Positive GSM36819 5.24095 6.02296 4.95004 5.97787 6.03835 5.70672GSM36820 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B GSM36820 Negative Positive GSM36820 4.40324 5.19518 4.67513 5.72457 6.95940 5.89659GSM36821 Luminal B Luminal B Luminal A UC Luminal B Luminal B GSM36821 Negative Positive GSM36821 5.50936 6.29064 5.52531 5.83042 6.00709 6.31195GSM36822 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36822 Negative Negative GSM36822 4.18190 2.06686 5.17199 6.32758 6.87977 6.00148GSM36823 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B GSM36823 Negative Positive GSM36823 5.27550 4.34510 5.97264 5.81681 7.14378 6.45559GSM36824 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36824 Negative Positive GSM36824 4.52063 2.96527 4.89240 5.77455 6.56723 5.87754GSM36825 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM36825 Negative Positive GSM36825 5.29583 5.68765 5.85979 5.87942 5.46426 5.53095GSM36826 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM36826 Negative Positive GSM36826 5.55388 2.75366 5.67670 6.06564 6.37093 5.77263GSM36827 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36827 Negative Negative GSM36827 4.11993 3.77735 5.45490 5.07267 6.96800 6.23598GSM36828 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36828 Negative Negative GSM36828 4.64733 2.63189 6.00320 5.78383 7.06296 6.29175GSM36829 Luminal B Luminal B HER2 UC Luminal B Luminal B GSM36829 Negative Positive GSM36829 5.10971 3.32504 5.12152 5.92426 7.32903 6.28368GSM36830 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36830 Negative Positive GSM36830 5.39055 1.98787 6.06746 6.19726 5.78136 5.58081GSM36831 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM36831 Negative Positive GSM36831 4.40288 1.84055 5.95015 5.68562 5.10352 4.44587GSM36832 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM36832 Negative Positive GSM36832 5.34594 4.30676 5.89754 5.48272 5.50979 5.51652GSM36833 Luminal B Luminal B HER2 HER2 HER2 HER2 GSM36833 Negative Negative GSM36833 4.61915 2.32239 7.58492 8.53110 6.87036 6.15631GSM36834 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B GSM36834 Negative Positive GSM36834 5.01707 2.87356 7.29899 8.08110 6.69109 6.18935GSM36835 HER2 HER2 Basal-like UC Basal-like Basal-like GSM36835 Negative Negative GSM36835 4.78966 1.88707 5.57900 5.36129 7.25170 6.29536GSM36836 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36836 Negative Positive GSM36836 4.84686 4.65586 6.03429 5.99943 5.77269 4.32444GSM36837 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36837 Negative Positive GSM36837 4.99096 2.28238 5.80212 5.65983 6.22535 5.75936GSM36838 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36838 Negative Positive GSM36838 5.26707 5.00930 5.37010 5.68765 6.51382 6.04767GSM36839 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM36839 Negative Positive GSM36839 5.37712 6.01445 6.16594 6.36613 5.28726 5.12844GSM36840 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM36840 Negative Positive GSM36840 4.98577 4.99856 4.67780 5.47017 5.89605 5.66470GSM36841 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36841 Negative Positive GSM36841 5.08198 5.52266 6.23050 6.10345 6.18970 5.64207GSM36842 Luminal B Luminal B HER2 HER2 Luminal A UC GSM36842 Negative Positive GSM36842 4.72458 6.16898 7.23400 6.30390 7.23317 5.54649GSM36843 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM36843 Negative Positive GSM36843 5.76603 6.60408 5.95569 6.56018 5.87746 5.66173GSM36844 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B GSM36844 Negative Positive GSM36844 4.67243 5.34568 4.49318 5.61750 7.23006 6.28208GSM36845 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36845 Negative Positive GSM36845 5.45826 5.36176 5.83529 6.23402 5.64792 5.53630GSM36846 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36846 Negative Negative GSM36846 4.69700 2.25129 5.30705 5.49635 6.70135 6.06237GSM36847 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36847 Negative Negative GSM36847 4.37199 4.03777 5.65767 5.82836 7.01822 6.42653GSM36848 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM36848 Negative Positive GSM36848 4.98334 4.64343 5.74354 5.69340 5.56567 4.80718GSM36849 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36849 Negative Positive GSM36849 5.83341 3.44362 5.57785 5.20070 6.23598 5.57797GSM36850 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM36850 Negative Positive GSM36850 5.20466 5.16421 4.86221 5.07392 6.00586 5.28076GSM36851 Luminal B Luminal B HER2 UC Luminal B Luminal B GSM36851 Negative Positive GSM36851 4.90977 1.68640 6.89421 7.15383 5.88638 5.82293GSM36852 Luminal B Luminal B Luminal A UC Luminal B Luminal B GSM36852 Negative Positive GSM36852 4.67258 4.00369 7.38761 7.65074 5.38220 5.51888GSM36853 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36853 Negative Positive GSM36853 5.21037 4.28909 5.25228 5.09742 5.59916 5.34767GSM36854 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36854 Negative Negative GSM36854 5.05104 2.51770 4.55843 5.50614 5.95894 5.80444GSM36855 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36855 Negative Negative GSM36855 4.40807 2.68785 5.06938 5.87718 6.61740 5.97638GSM36856 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM36856 Negative Positive GSM36856 5.13350 5.73042 6.15843 5.42935 6.38688 5.32196GSM36857 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM36857 Negative Positive GSM36857 5.43913 4.95723 5.75899 6.16395 6.16331 5.84966GSM36858 Luminal B Luminal B Luminal A UC Luminal B Luminal B GSM36858 Negative Positive GSM36858 5.19601 2.78501 7.11569 6.83174 6.83346 6.09795GSM36859 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM36859 Negative Positive GSM36859 4.91377 5.62113 5.58652 5.87465 5.54869 5.29223GSM36860 Luminal B Luminal B HER2 UC Luminal B Luminal B GSM36860 Negative Positive GSM36860 4.23217 5.15271 7.05702 7.08028 6.86066 5.96918GSM36861 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM36861 Negative Positive GSM36861 5.27305 5.73010 5.33248 6.27627 5.26992 5.63017GSM36862 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36862 Negative Negative GSM36862 4.44879 2.27213 5.13928 5.79849 6.90615 5.84480GSM36863 Luminal B Luminal B HER2 UC Luminal B Luminal B GSM36863 Negative Negative GSM36863 4.38734 4.69226 5.86207 6.02393 6.35975 6.17861GSM36864 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM36864 Negative Positive GSM36864 5.34731 4.73883 6.04684 6.40241 6.27740 5.92653GSM36865 Luminal B Luminal B Basal-like Basal-like Basal-like Basal-like GSM36865 Negative Negative GSM36865 4.40871 4.00369 5.53459 5.53733 6.79872 6.21223GSM36866 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM36866 Negative Positive GSM36866 7.21020 5.90509 6.38845 6.31300 5.83247 5.53726GSM36867 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36867 Negative Positive GSM36867 6.17396 6.27420 6.20400 6.18436 6.10009 5.78755GSM36868 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM36868 Negative Positive GSM36868 5.07249 5.81144 5.62407 4.91118 5.52106 4.49180GSM36869 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM36869 Negative Positive GSM36869 5.35714 4.34381 5.22985 5.41699 5.39272 5.15954GSM36870 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B GSM36870 Negative Positive GSM36870 5.26557 2.02815 5.68510 5.87914 6.87534 5.95326GSM36871 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM36871 Negative Positive GSM36871 4.83407 5.04019 5.49230 5.14575 4.79991 5.06872GSM36872 Luminal B UC HER2 UC Luminal B Luminal B GSM36872 Negative Positive GSM36872 5.35822 2.73437 6.81856 7.25255 6.67380 5.88712GSM36873 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36873 Negative Positive GSM36873 5.06513 4.76984 4.85402 6.14676 6.07258 6.02542GSM36874 Luminal B UC Luminal A Luminal A Luminal B Luminal B GSM36874 Negative Positive GSM36874 5.12891 5.01728 5.25797 4.68120 6.22337 5.52552GSM36875 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36875 Negative Negative GSM36875 4.32789 4.31348 4.91319 3.98341 6.87668 6.56916GSM36876 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36876 Negative Negative GSM36876 4.86513 2.63189 5.35383 5.91620 7.11785 5.91049GSM36877 Luminal B Luminal B HER2 UC Luminal B Luminal B GSM36877 Negative Positive GSM36877 4.60807 2.52573 4.25470 5.94490 6.67708 5.86729GSM36878 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36878 Negative Positive GSM36878 5.10926 4.99315 5.19389 6.00660 6.46568 5.86190GSM36879 HER2 HER2 HER2 HER2 HER2 HER2 GSM36879 Negative Negative GSM36879 4.69457 2.00148 6.69951 7.95525 6.29286 5.71025GSM36880 Luminal B UC Luminal A Luminal A Luminal B Luminal B GSM36880 Negative Positive GSM36880 4.65988 3.01062 5.27007 5.48355 6.46474 5.11108GSM36881 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B GSM36881 Negative Positive GSM36881 5.17891 3.00072 5.24032 5.37713 7.55176 5.37190GSM36882 Luminal B UC Luminal A Luminal A Normal breast-like Normal breast-like GSM36882 Negative Positive GSM36882 5.20810 5.19573 5.94518 5.47897 5.10595 5.30426GSM36883 Luminal B UC Luminal A Luminal A Luminal A Luminal A GSM36883 Negative Positive GSM36883 4.74080 3.54962 5.33429 6.34774 5.25437 5.70950GSM36884 Luminal B Luminal B HER2 HER2 Luminal B Luminal B GSM36884 Negative Positive GSM36884 4.77925 2.58022 7.58182 8.00890 6.27344 6.13706GSM36885 Luminal A Luminal A Luminal A Luminal A Normal breast-like Normal breast-like GSM36885 Negative Positive GSM36885 4.68225 6.28842 5.12094 5.92986 5.45190 4.85353GSM36886 Luminal B Luminal B HER2 UC Basal-like Basal-like GSM36886 Negative Negative GSM36886 4.57050 2.18605 4.73192 4.63279 6.50144 5.82775GSM36887 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36887 Negative Positive GSM36887 5.02951 2.90142 5.11836 4.48300 5.59471 5.27135GSM36888 Luminal B Luminal B HER2 UC Luminal B Luminal B GSM36888 Negative Positive GSM36888 5.16272 1.33500 5.04644 4.47278 6.35193 5.47475GSM36889 Luminal B Luminal B Luminal A UC Luminal B Luminal B GSM36889 Negative Positive GSM36889 4.89922 2.91777 5.44910 4.68398 5.88277 5.71790

Supplementary Table 6: Molecular subtype assignment of 286 breast cancers (‘Wang’) 9 using the single sample predictors by Sorlie et al4, Hu et al5 and Parker et al6 using HUGO gene symbol for probe mapping and averaging of multiple probes identified to match a gene in a centroid/SSP; and ER and lymph node status, and microarray-based mRNA expression of ESR1 , PGR , ERBB2 , GRB7 , AURKA and MKI67 .

14

GSM36890 Luminal B Luminal B HER2 UC Normal breast-like Normal breast-like GSM36890 Negative Positive GSM36890 4.82347 2.44235 5.48032 5.35611 6.17504 5.70401GSM36891 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36891 Negative Negative GSM36891 4.61963 2.00148 5.84406 5.62870 6.38334 5.66415GSM36892 Luminal B Luminal B HER2 UC Luminal B Luminal B GSM36892 Negative Positive GSM36892 4.20436 4.32281 5.68544 5.70011 6.44095 5.20444GSM36893 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM36893 Negative Positive GSM36893 4.95384 1.82455 6.26598 5.73269 6.38890 5.28559GSM36894 Luminal B UC Luminal A Luminal A Luminal A UC GSM36894 Negative Positive GSM36894 4.74361 3.49953 6.20973 5.92613 5.65038 5.60312GSM36895 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36895 Negative Positive GSM36895 5.37732 2.20827 6.19080 5.99321 6.03500 5.63596GSM36896 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36896 Negative Positive GSM36896 5.33178 5.42935 6.47054 6.32149 5.44328 5.30805GSM36897 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM36897 Negative Positive GSM36897 5.57886 4.08092 6.07659 5.27402 6.23735 5.53043GSM36898 Luminal B UC Luminal A UC Luminal B Luminal B GSM36898 Negative Positive GSM36898 5.12066 3.89386 5.99347 5.49758 6.79223 5.60452GSM36899 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B GSM36899 Negative Positive GSM36899 4.99619 2.70136 5.98846 5.37389 6.95721 6.25693GSM36900 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36900 Negative Positive GSM36900 4.81745 4.16044 4.91370 4.08933 6.65647 5.92575GSM36901 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36901 Negative Positive GSM36901 4.30601 3.05871 4.60506 5.61020 6.56541 6.35551GSM36902 Basal-like UC Basal-like UC Normal breast-like Normal breast-like GSM36902 Negative Positive GSM36902 4.39323 3.96462 5.04415 5.71801 5.62474 5.45770GSM36903 Luminal B Luminal B Luminal A UC Luminal B Luminal B GSM36903 Negative Positive GSM36903 4.44369 1.90211 4.88260 5.20236 6.93323 5.96633GSM36904 Luminal B Luminal B HER2 HER2 HER2 HER2 GSM36904 Negative Negative GSM36904 4.10882 1.64866 7.26539 7.78422 6.62936 5.71626GSM36905 Luminal B Luminal B Luminal A UC Luminal B Luminal B GSM36905 Negative Negative GSM36905 4.60822 1.58924 4.86876 4.92725 6.17794 5.68387GSM36906 Luminal B Luminal B Basal-like UC Luminal B Luminal B GSM36906 Negative Negative GSM36906 4.28146 2.67415 5.55644 5.31321 6.57200 6.01882GSM36907 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM36907 Negative Positive GSM36907 4.95229 6.06564 5.86656 5.58537 6.28283 5.64589GSM36908 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36908 Negative Positive GSM36908 5.41807 5.28473 5.86010 5.19018 6.78389 6.16086GSM36909 HER2 UC Luminal A UC Normal breast-like Normal breast-like GSM36909 Negative Negative GSM36909 3.82113 1.28093 5.67493 5.24122 5.08698 4.88558GSM36910 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM36910 Negative Positive GSM36910 5.28894 5.97939 5.22135 5.50085 5.61786 4.95910GSM36911 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36911 Negative Positive GSM36911 5.56149 1.90211 6.05668 6.08290 6.01029 5.53091GSM36912 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36912 Negative Negative GSM36912 3.54252 1.84055 4.89692 5.70611 7.31162 6.17684GSM36913 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM36913 Negative Positive GSM36913 5.14994 2.31254 5.78508 5.69373 5.75130 5.48379GSM36914 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM36914 Negative Positive GSM36914 4.84686 5.39544 5.20223 5.79332 5.94647 5.54720GSM36915 Luminal B Luminal B HER2 HER2 Normal breast-like UC GSM36915 Negative Negative GSM36915 4.32339 2.74084 7.09247 7.01266 6.37877 5.73813GSM36916 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM36916 Negative Positive GSM36916 4.71796 5.13874 5.68944 5.80483 5.23164 4.39194GSM36917 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM36917 Negative Positive GSM36917 5.22817 3.21888 4.90933 4.70953 6.09199 5.16825GSM36918 Basal-like UC Basal-like UC Basal-like Basal-like GSM36918 Negative Negative GSM36918 4.97804 1.54756 5.48371 5.54048 6.77285 5.49725GSM36919 Luminal B UC Luminal A Luminal A Luminal A Luminal A GSM36919 Negative Positive GSM36919 4.57228 6.37911 6.04059 5.32447 6.12621 5.39960GSM36920 Luminal B Luminal B Luminal A UC Luminal B Luminal B GSM36920 Negative Positive GSM36920 4.60160 5.34663 6.58880 6.45315 5.77920 5.73311GSM36921 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36921 Negative Positive GSM36921 4.87981 5.37064 6.07796 4.85281 6.42633 5.45780GSM36922 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM36922 Negative Positive GSM36922 6.14876 1.80829 5.76845 6.15231 6.04761 5.56332GSM36923 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36923 Negative Negative GSM36923 3.90772 1.98787 5.18124 6.33079 6.51115 5.85545GSM36924 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36924 Negative Positive GSM36924 5.65818 4.57471 5.45203 5.91782 6.84832 5.47767GSM36925 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM36925 Negative Positive GSM36925 4.82290 5.08078 5.68147 6.28674 5.76362 5.43699GSM36926 HER2 HER2 HER2 UC Luminal B Luminal B GSM36926 Negative Negative GSM36926 3.73932 1.68640 6.76324 7.23914 6.43807 5.65795GSM36927 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36927 Negative Positive GSM36927 4.26897 1.93152 5.65136 3.71844 6.52723 5.83254GSM36928 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM36928 Negative Positive GSM36928 4.64040 2.55723 4.96155 5.82659 5.75701 5.10481GSM36929 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM36929 Negative Positive GSM36929 4.88029 2.92316 5.98647 6.08927 6.13578 5.88588GSM36930 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM36930 Negative Positive GSM36930 5.72424 4.56017 7.19015 7.15883 5.99246 5.65270GSM36931 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36931 Negative Positive GSM36931 4.46376 1.88707 5.17292 5.34281 6.31192 5.92250GSM36932 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM36932 Negative Positive GSM36932 5.01672 1.97408 4.78389 5.94908 5.25906 4.95463GSM36933 Luminal B Luminal B Luminal A UC Luminal B Luminal B GSM36933 Negative Positive GSM36933 5.33389 3.08191 5.90021 5.82008 5.91053 6.17292GSM36934 Luminal B Luminal B HER2 UC Luminal B Luminal B GSM36934 Negative Positive GSM36934 5.12612 4.07754 7.18483 6.63345 7.10455 5.96018GSM36935 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36935 Negative Negative GSM36935 4.20238 1.62924 5.56439 5.79179 6.38046 6.16673GSM36936 Luminal B UC Luminal A Luminal A Luminal A Luminal A GSM36936 Negative Positive GSM36936 4.82778 2.86220 5.38689 5.91269 5.15560 4.87792GSM36937 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36937 Negative Negative GSM36937 4.44272 4.35157 5.75782 5.83890 7.11639 6.16574GSM36938 Luminal B UC Luminal A Luminal A Luminal B Luminal B GSM36938 Negative Positive GSM36938 4.88672 4.71671 5.94773 4.99315 5.90781 5.18322GSM36939 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B GSM36939 Negative Positive GSM36939 5.30308 5.43547 4.61674 4.55913 7.02331 6.27862GSM36940 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36940 Negative Negative GSM36940 4.27745 3.78419 5.35004 5.34854 6.77342 5.77688GSM36941 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36941 Negative Negative GSM36941 4.00449 4.04130 5.63546 5.64580 5.86873 6.46128GSM36942 Luminal B Luminal B Luminal A UC Luminal A Luminal A GSM36942 Negative Positive GSM36942 4.78287 5.70278 5.48268 4.68951 5.80121 4.61997GSM36943 Luminal A UC Luminal A Luminal A Luminal B Luminal B GSM36943 Negative Positive GSM36943 5.05224 2.04122 5.36452 5.59620 6.68060 5.64203GSM36944 Luminal B UC Luminal A Luminal A Luminal A UC GSM36944 Negative Positive GSM36944 4.70731 5.86164 5.50508 3.85439 5.80333 5.23683GSM36945 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM36945 Negative Positive GSM36945 5.81398 5.66192 5.81958 5.77672 5.56145 5.69436GSM36946 Luminal A Luminal A Luminal B Luminal B Luminal B Luminal B GSM36946 Negative Positive GSM36946 5.31157 5.09314 6.02840 5.68154 6.81685 5.72114GSM36947 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B GSM36947 Negative Positive GSM36947 4.60788 2.29253 5.41959 5.65073 6.90655 6.45063GSM36948 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM36948 Negative Positive GSM36948 5.27093 2.74727 5.57879 5.77827 6.10903 5.78098GSM36949 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36949 Negative Negative GSM36949 4.02360 2.02815 4.13083 4.91706 7.04071 6.70308GSM36950 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36950 Negative Positive GSM36950 5.23565 5.35517 5.12972 5.72945 6.33877 5.68941GSM36951 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36951 Negative Positive GSM36951 5.55625 6.29064 6.06943 6.15380 6.18105 5.74118GSM36952 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36952 Negative Negative GSM36952 5.03487 2.63189 4.76570 5.65073 6.02972 6.19991GSM36953 Luminal B Luminal B HER2 HER2 Luminal B UC GSM36953 Negative Negative GSM36953 4.58227 2.96527 6.19323 6.32472 6.64860 5.83175GSM36954 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B GSM36954 Negative Positive GSM36954 5.29278 2.30259 5.38542 5.99745 7.38250 5.61519GSM36955 Luminal B UC HER2 UC Luminal B Luminal B GSM36955 Negative Negative GSM36955 4.17402 3.62167 5.30976 5.63229 6.23813 5.87713GSM36956 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM36956 Negative Positive GSM36956 5.21950 6.26966 5.38514 4.49088 7.07800 6.25857GSM36957 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM36957 Negative Positive GSM36957 5.07219 4.57058 5.52651 5.50655 5.68017 5.04298GSM36958 Luminal B UC Luminal A UC Normal breast-like Normal breast-like GSM36958 Negative Positive GSM36958 4.32080 5.03955 5.69017 4.58190 5.66712 5.54768GSM36959 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36959 Negative Negative GSM36959 3.74108 1.38629 4.93398 5.76988 7.11769 6.18640GSM36960 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36960 Negative Positive GSM36960 4.22711 1.68640 5.95451 4.91779 6.62087 5.90793GSM36961 Luminal B UC HER2 UC HER2 HER2 GSM36961 Negative Negative GSM36961 4.32341 3.19458 6.36628 6.03261 6.59728 5.93641GSM36962 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM36962 Negative Positive GSM36962 5.12024 6.29619 5.15122 5.45618 5.31910 4.82106GSM36963 Luminal B Luminal B Luminal A UC Luminal B Luminal B GSM36963 Negative Positive GSM36963 4.69082 4.90897 6.20533 6.54779 6.49269 5.80765GSM36964 HER2 HER2 HER2 HER2 HER2 HER2 GSM36964 Negative Negative GSM36964 4.14372 1.62924 7.40589 7.52542 6.21780 6.19118GSM36965 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36965 Negative Positive GSM36965 4.95647 4.53260 5.25168 4.91192 6.41739 5.26086GSM36966 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36966 Negative Negative GSM36966 3.90826 1.74047 5.40222 5.89495 6.32561 5.55806GSM36967 Luminal B UC Luminal A Luminal A Luminal B Luminal B GSM36967 Negative Positive GSM36967 5.20689 1.85630 4.94113 5.62906 6.70723 5.51382GSM36968 Luminal B Luminal B HER2 HER2 HER2 HER2 GSM36968 Negative Negative GSM36968 4.14314 2.12823 6.97500 7.76980 7.16627 5.74971GSM36969 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36969 Negative Negative GSM36969 4.21065 2.30259 4.24227 5.97024 7.12351 6.26122GSM36970 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36970 Negative Positive GSM36970 5.28772 3.95508 4.88920 5.47605 5.35517 4.35929GSM36971 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM36971 Negative Positive GSM36971 4.91912 4.45551 5.06043 4.99451 6.03141 5.24495GSM36972 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM36972 Negative Positive GSM36972 4.61079 2.87356 6.14983 5.95142 6.07649 5.55040GSM36973 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36973 Negative Positive GSM36973 5.98756 6.07764 5.62713 6.40704 6.13448 5.49372GSM36974 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B GSM36974 Negative Positive GSM36974 5.36447 1.56862 5.56364 5.90181 7.11485 5.89574GSM36975 Luminal B Luminal B HER2 UC Luminal B Luminal B GSM36975 Negative Positive GSM36975 4.76655 3.47507 6.64274 7.51747 6.17170 5.54154GSM36976 Luminal B UC Luminal A Luminal A Luminal A Luminal A GSM36976 Negative Positive GSM36976 5.48041 5.77082 5.87929 5.08698 6.25517 5.57004GSM36977 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36977 Negative Negative GSM36977 4.71137 1.33500 5.59469 5.11500 7.02669 5.95329GSM36978 HER2 HER2 Luminal A UC Normal breast-like Normal breast-like GSM36978 Negative Negative GSM36978 4.91480 1.70475 7.18397 7.78734 6.15528 5.68748GSM36979 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM36979 Negative Positive GSM36979 5.04792 4.41522 5.83399 5.64049 7.44828 5.74445GSM36980 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM36980 Negative Positive GSM36980 5.53383 5.73947 5.44100 6.65827 5.69776 5.59070GSM36981 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36981 Negative Negative GSM36981 3.65624 2.45959 5.58761 5.93225 6.50504 6.39272GSM36982 Luminal B UC Luminal A Luminal A Normal breast-like Normal breast-like GSM36982 Negative Positive GSM36982 4.83064 4.57574 5.92259 6.27061 5.81652 5.66806GSM36983 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM36983 Negative Positive GSM36983 5.28590 5.34186 5.15775 5.79758 5.55257 5.49089GSM36984 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36984 Negative Positive GSM36984 6.98706 2.64617 6.32308 6.03237 5.82423 5.92176GSM36985 Luminal B Luminal B Luminal B UC Luminal B Luminal B GSM36985 Negative Positive GSM36985 4.95760 4.22829 5.54738 5.40538 6.91820 5.90404GSM36986 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36986 Negative Positive GSM36986 4.71780 1.66771 5.13864 6.17711 5.96075 5.15046GSM36987 Luminal B UC Luminal A Luminal A Luminal A UC GSM36987 Negative Positive GSM36987 4.46291 5.12871 4.62645 5.70278 6.42697 5.54944GSM36988 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36988 Negative Positive GSM36988 5.09608 5.22359 5.18488 5.79697 5.79210 5.34138GSM36989 Luminal B Luminal B Luminal A UC Luminal B Luminal B GSM36989 Negative Positive GSM36989 4.66447 2.37024 5.43905 5.64651 6.74205 5.46885GSM36990 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36990 Negative Positive GSM36990 5.52689 5.08140 5.59417 5.80393 5.64084 4.75837GSM36991 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM36991 Negative Negative GSM36991 3.85175 2.27213 5.62837 5.39907 6.73471 6.08851GSM36992 Luminal B Luminal B HER2 HER2 HER2 HER2 GSM36992 Negative Positive GSM36992 4.14865 1.45862 8.23643 8.76755 6.69134 5.72504GSM36993 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM36993 Negative Positive GSM36993 4.83037 2.74727 5.75689 5.63336 4.82991 4.88311GSM36994 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM36994 Negative Positive GSM36994 5.03539 4.59411 4.35978 5.50614 5.10473 4.95878GSM36995 Luminal B Luminal B HER2 UC Luminal B Luminal B GSM36995 Negative Positive GSM36995 4.77697 5.03500 7.20717 7.29512 7.12536 6.17772GSM36996 Luminal B Luminal B HER2 HER2 Luminal B Luminal B GSM36996 Negative Positive GSM36996 4.59100 3.73529 6.35923 6.45347 6.34001 5.85470GSM36997 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM36997 Negative Positive GSM36997 4.97656 2.53370 5.42497 3.25810 6.73661 5.95857GSM36998 Luminal B UC Luminal A Luminal A Luminal A Luminal A GSM36998 Negative Positive GSM36998 4.96068 5.52466 5.71191 6.12337 5.74172 5.13805GSM36999 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM36999 Negative Positive GSM36999 5.75865 4.91925 5.41962 5.96947 6.01494 5.49077GSM37000 Luminal B UC Luminal A Luminal A Luminal A Luminal A GSM37000 Negative Positive GSM37000 4.55858 5.44068 5.64104 5.98821 5.39272 5.09158GSM37001 Luminal B Luminal B Luminal A Luminal A Luminal A Luminal A GSM37001 Negative Positive GSM37001 4.64360 1.91692 7.54660 7.33387 5.76237 5.45115GSM37002 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM37002 Negative Negative GSM37002 4.45168 3.03495 5.30457 5.79271 6.82882 6.07440GSM37003 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B GSM37003 Negative Positive GSM37003 4.60733 2.66723 4.90639 4.14789 7.42351 6.07016GSM37004 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM37004 Negative Positive GSM37004 6.83433 1.85630 5.86660 5.82393 6.22693 5.87509GSM37005 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM37005 Negative Positive GSM37005 5.20029 5.65669 5.73456 6.01616 6.27004 5.57595GSM37006 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B GSM37006 Negative Positive GSM37006 5.17546 3.13549 5.86089 5.95791 7.26913 5.79569GSM37007 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM37007 Negative Positive GSM37007 4.96575 2.77882 5.77080 5.69609 6.38637 6.10912

15

GSM37008 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM37008 Negative Positive GSM37008 5.07430 1.96009 5.29400 5.64403 6.00216 5.56147GSM37009 Luminal A UC Luminal A UC Luminal B Luminal B GSM37009 Negative Positive GSM37009 5.21718 5.03305 5.56615 5.56375 6.24436 5.45272GSM37010 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM37010 Negative Positive GSM37010 5.81017 6.34318 5.42453 6.09402 6.40159 5.78941GSM37011 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM37011 Negative Positive GSM37011 5.89388 6.08404 6.45245 6.11169 5.91674 5.54559GSM37012 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM37012 Negative Positive GSM37012 5.40781 5.86392 6.20049 6.36337 5.54947 5.45006GSM37013 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM37013 Negative Positive GSM37013 5.13408 2.27213 5.75861 6.12359 6.01591 5.55143GSM37014 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM37014 Negative Positive GSM37014 5.51880 2.44235 5.92581 6.11058 6.75809 6.22016GSM37015 Luminal B UC Luminal A Luminal A Luminal A Luminal A GSM37015 Negative Positive GSM37015 4.92201 5.08327 6.28593 6.44127 5.68731 5.58021GSM37016 Luminal B Luminal B HER2 HER2 HER2 HER2 GSM37016 Negative Negative GSM37016 4.60898 2.15176 7.45979 6.57967 6.74170 6.76487GSM37017 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM37017 Negative Negative GSM37017 4.14718 2.05412 5.64085 5.92906 6.76388 5.92811GSM37018 Luminal B Luminal B Luminal B UC Luminal B Luminal B GSM37018 Negative Positive GSM37018 4.93853 3.78191 5.04266 5.26631 6.35611 6.33614GSM37019 Luminal B UC Luminal A Luminal A Normal breast-like UC GSM37019 Negative Positive GSM37019 4.33926 5.11680 6.14720 5.84615 6.16940 5.51791GSM37020 Luminal B Luminal B HER2 HER2 HER2 HER2 GSM37020 Negative Negative GSM37020 4.46603 1.75786 7.26651 7.47369 7.19346 5.64703GSM37021 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM37021 Negative Negative GSM37021 4.01105 1.68640 5.38294 5.25593 7.21015 6.64836GSM37022 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM37022 Negative Negative GSM37022 4.33498 1.54756 5.35274 5.50044 6.48050 5.42118GSM37023 Luminal B Luminal B HER2 HER2 HER2 HER2 GSM37023 Negative Negative GSM37023 4.33043 2.67415 7.45426 8.68069 6.57214 5.81739GSM37024 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM37024 Negative Positive GSM37024 5.32319 6.32651 6.22469 6.37417 5.35659 5.57638GSM37025 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM37025 Negative Positive GSM37025 5.24325 5.07079 6.04280 5.81264 5.79027 5.47970GSM37026 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM37026 Negative Positive GSM37026 5.02054 4.58904 5.85547 5.94777 5.54985 5.55771GSM37027 Luminal B Luminal B Luminal A UC Luminal B Luminal B GSM37027 Negative Positive GSM37027 5.02119 2.75366 5.25972 5.99271 6.61526 5.52391GSM37028 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM37028 Negative Positive GSM37028 6.39515 7.01058 5.71245 6.40638 5.51946 5.34200GSM37029 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM37029 Negative Positive GSM37029 5.31978 2.05412 6.08906 5.93701 6.36027 5.38723GSM37030 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM37030 Negative Positive GSM37030 5.65436 2.88480 5.93949 6.22396 5.69441 5.92749GSM37031 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM37031 Negative Positive GSM37031 4.75560 3.06805 6.80867 6.72395 6.47790 6.17666GSM37032 Luminal B Luminal B Luminal A Luminal A Luminal A Luminal A GSM37032 Negative Positive GSM37032 4.61228 2.37955 6.17944 5.79758 5.88444 5.40409GSM37033 Luminal B Luminal B Luminal A Luminal A Luminal A Luminal A GSM37033 Negative Positive GSM37033 4.94839 5.90917 6.57700 6.19359 6.48753 5.62543GSM37034 Luminal B Luminal B HER2 HER2 HER2 HER2 GSM37034 Negative Negative GSM37034 4.29311 2.74727 6.99282 6.74146 6.42859 6.14473GSM37035 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B GSM37035 Negative Positive GSM37035 5.43429 4.89933 5.61399 5.77269 7.26990 6.13229GSM37036 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM37036 Negative Positive GSM37036 4.81259 2.07944 7.85664 8.25533 5.90509 5.83267GSM37037 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM37037 Negative Positive GSM37037 6.17292 3.05871 6.53359 5.95194 6.05044 5.39153GSM37038 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B GSM37038 Negative Positive GSM37038 5.26270 5.82216 5.98228 5.71834 6.98416 5.59791GSM37039 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM37039 Negative Positive GSM37039 4.89170 2.90690 5.71631 5.92265 5.93648 5.57073GSM37040 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM37040 Negative Negative GSM37040 4.22631 3.89182 4.66335 5.60138 6.68748 6.31506GSM37041 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM37041 Negative Positive GSM37041 4.76611 5.37296 6.19160 5.53930 6.45252 5.11366GSM37042 HER2 UC HER2 HER2 Luminal B Luminal B GSM37042 Negative Negative GSM37042 4.32983 1.62924 8.15182 7.76294 6.13079 6.04472GSM37043 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM37043 Negative Negative GSM37043 4.32269 4.26409 5.25643 5.61495 6.76861 6.41410GSM37044 Luminal A UC Luminal A Luminal A Luminal B Luminal B GSM37044 Negative Positive GSM37044 4.85340 2.51770 6.03514 6.32704 5.06386 5.41950GSM37045 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM37045 Negative Negative GSM37045 4.42101 1.91692 4.76049 5.88388 7.14929 6.22299GSM37046 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM37046 Negative Positive GSM37046 4.77346 2.61007 6.07781 5.71966 5.62149 4.98199GSM37047 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM37047 Negative Positive GSM37047 4.54093 2.96011 5.72935 5.54479 6.74429 6.17122GSM37048 Basal-like Basal-like Basal-like UC Normal breast-like Normal breast-like GSM37048 Negative Negative GSM37048 4.63973 2.39790 5.36559 6.28245 5.63085 5.54678GSM37049 Luminal B Luminal B HER2 UC Luminal B Luminal B GSM37049 Negative Negative GSM37049 4.75891 2.86790 5.59946 6.86829 6.04358 5.53521GSM37050 Luminal B Luminal B Basal-like UC Basal-like Basal-like GSM37050 Negative Negative GSM37050 4.29738 2.99072 5.22869 4.97466 5.64686 5.81616GSM37051 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM37051 Negative Positive GSM37051 4.49385 2.61740 5.58929 5.32933 6.22019 5.87711GSM37052 HER2 HER2 HER2 HER2 Basal-like UC GSM37052 Negative Negative GSM37052 4.51448 3.02529 6.76264 6.80239 6.59619 5.51632GSM37053 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM37053 Negative Negative GSM37053 4.27799 4.17899 4.77949 5.77765 6.73483 5.64489GSM37054 Luminal B Luminal B HER2 HER2 Luminal B Luminal B GSM37054 Negative Negative GSM37054 4.66772 3.62167 8.53817 8.25910 6.55279 6.47349GSM37055 Luminal B Luminal B HER2 HER2 HER2 HER2 GSM37055 Negative Negative GSM37055 4.51377 5.77300 7.44006 7.83201 6.41198 5.77113GSM37056 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM37056 Negative Negative GSM37056 5.42787 4.89485 5.99600 5.86164 5.62582 5.30404GSM37057 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM37057 Negative Positive GSM37057 5.18851 3.19867 5.09001 5.31222 6.16919 5.90266GSM37058 Luminal B Luminal B Luminal A UC Luminal B Luminal B GSM37058 Negative Positive GSM37058 4.64939 1.80829 4.35507 5.87830 6.29545 5.60393GSM37059 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM37059 Negative Positive GSM37059 5.42491 2.81541 5.61581 5.60507 5.39907 5.09266GSM37060 Luminal B Luminal B Luminal A Luminal A Luminal A Luminal A GSM37060 Negative Positive GSM37060 5.08320 5.67573 6.54362 6.21501 6.18497 5.87083GSM37061 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM37061 Negative Negative GSM37061 5.19694 4.96842 5.80283 6.10725 5.51986 4.87263GSM37062 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM37062 Negative Positive GSM37062 4.70047 5.10230 5.07193 5.63085 6.98869 6.04295


16




Sample ID Tumour diameter (cm)

Lymph node status ER status Histological grade Age (years) Sample ID ESR1 gene expression (probe average)






GSM177885 HER2 UC HER2 UC Luminal B Luminal B GSM177885 3 Negative Negative 3 57 GSM177885 3.53963 2.95736 5.83526 4.69484 6.66518 5.49308GSM177886 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B GSM177886 3 Negative Positive 3 57 GSM177886 5.68774 4.63356 5.16121 5.01794 7.24788 5.67611GSM177887 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM177887 2.5 Negative Negative 3 48 GSM177887 3.51982 3.41218 5.39341 5.72911 7.10683 5.54566GSM177888 Luminal B Luminal B HER2 HER2 Luminal B Luminal B GSM177888 1.8 Negative Positive 3 42 GSM177888 5.42211 4.99791 6.10364 4.97099 6.68539 5.30782GSM177889 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM177889 3 Negative Positive 2 46 GSM177889 5.57108 1.50692 5.70865 5.59070 5.84814 4.75010GSM177890 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM177890 2 Negative Positive 2 58 GSM177890 4.97283 1.18395 6.08345 4.78377 5.56375 4.80538GSM177891 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM177891 2 Negative Negative 3 44 GSM177891 3.85386 3.27459 5.90230 5.36778 7.60529 5.68211GSM177892 Luminal B UC Luminal A Luminal A Luminal A Luminal A GSM177892 2.5 Negative Positive 1 58 GSM177892 5.74111 1.25359 5.68013 5.04777 5.60284 5.08264GSM177893 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM177893 3 Negative Positive 3 47 GSM177893 6.43539 6.77418 6.55793 5.04275 5.89173 4.86751GSM177894 Luminal B UC Luminal A Luminal A Normal breast-like Normal breast-like GSM177894 2.5 Negative Positive 2 38 GSM177894 5.08764 2.77441 5.89405 5.12841 6.02863 5.62967GSM177895 Luminal B Luminal B Luminal A UC Luminal B Luminal B GSM177895 2 Negative Positive 3 59 GSM177895 5.71906 4.65253 8.37230 7.03922 6.44279 5.70924GSM177896 Luminal B UC Luminal A Luminal A Luminal A Luminal A GSM177896 0.8 Negative Positive 1 50 GSM177896 4.80705 6.92446 6.35334 3.94659 5.62788 5.06592GSM177897 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM177897 4.5 Negative Negative 3 46 GSM177897 3.64314 2.07738 5.62221 5.73125 6.74776 6.30177GSM177898 HER2 UC Luminal A UC Luminal B UC GSM177898 2 Negative Negative 2 57 GSM177898 3.79194 1.49555 6.02499 5.18025 5.65437 5.14768GSM177899 Luminal B Luminal B HER2 HER2 Luminal B Luminal B GSM177899 2.5 Negative Negative 3 33 GSM177899 3.87885 1.54705 5.64352 5.22811 7.52490 5.10837GSM177900 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B GSM177900 2 Negative Positive 3 42 GSM177900 6.33008 1.87034 6.40235 5.70689 5.83118 5.41754GSM177901 Luminal B Luminal B HER2 UC Basal-like Basal-like GSM177901 2 Negative Negative 3 38 GSM177901 4.70185 5.36413 4.35155 4.51841 6.23254 5.46093GSM177902 Luminal B Luminal B HER2 HER2 HER2 HER2 GSM177902 2.5 Negative Negative 2 55 GSM177902 3.30342 1.51944 8.19829 7.51115 5.80528 5.37136GSM177903 Luminal B Luminal B HER2 UC Luminal B Luminal B GSM177903 2.5 Negative Negative 2 57 GSM177903 4.08873 0.73914 6.48448 5.60863 6.16531 5.47791GSM177904 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM177904 2.5 Negative Positive 2 46 GSM177904 5.44434 6.85189 6.00243 5.31980 5.30052 5.37208GSM177905 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM177905 2 Negative Positive 2 50 GSM177905 4.98457 4.52317 5.66119 4.96932 5.92920 4.81706GSM177906 Basal-like Basal-like Basal-like UC Basal-like Basal-like GSM177906 2 Negative Negative 3 46 GSM177906 3.14478 3.87878 4.71481 5.55536 7.10240 6.79790GSM177907 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM177907 2.5 Negative Positive 2 46 GSM177907 5.52168 6.00903 5.72254 5.47917 5.58157 4.80216GSM177908 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM177908 1.5 Negative Positive 2 51 GSM177908 6.07699 6.52863 6.94256 5.94729 6.09361 5.49823GSM177909 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM177909 2.5 Negative Negative 3 58 GSM177909 3.91476 2.32650 5.22423 5.11225 6.16090 5.93392GSM177910 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM177910 2.6 Negative Positive 1 59 GSM177910 6.51221 5.85507 6.19341 5.65297 6.04060 4.98580GSM177911 Luminal B Luminal B Luminal A Luminal A Luminal A Luminal A GSM177911 0.6 Negative Positive 2 49 GSM177911 5.37994 3.71667 6.09749 5.33974 4.93546 3.74819GSM177912 Normal breast-like UC Luminal A Luminal A Normal breast-like Normal breast-like GSM177912 2.5 Negative Positive 1 43 GSM177912 5.25459 4.89345 5.75885 5.85899 5.29161 4.90466GSM177913 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM177913 2 Negative Negative 3 47 GSM177913 3.81906 2.03394 6.05352 5.72122 6.77334 5.90507GSM177914 Luminal B Luminal B Luminal A Luminal A Luminal A Luminal A GSM177914 1.7 Negative Positive 3 37 GSM177914 5.22411 4.69713 4.94368 5.24610 5.41777 4.78480GSM177915 Luminal B Luminal B Luminal A UC Luminal B Luminal B GSM177915 4 Negative Positive 3 48 GSM177915 4.65021 4.87062 6.87873 6.22884 6.64925 5.14602GSM177916 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM177916 1.9 Negative Positive 2 47 GSM177916 5.20376 5.59780 4.75195 5.14317 6.68366 5.55975GSM177917 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM177917 2.5 Negative Positive 2 46 GSM177917 5.49242 6.07129 6.14080 5.61192 5.76640 5.37462GSM177918 HER2 HER2 HER2 HER2 HER2 HER2 GSM177918 2 Negative Negative 3 48 GSM177918 4.10241 3.92625 7.06596 6.89974 6.40545 5.43293GSM177919 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM177919 1.9 Negative Positive 2 58 GSM177919 6.43426 7.04943 5.71367 5.36868 5.54632 4.35993GSM177920 Luminal B UC Luminal A Luminal A Luminal B Luminal B GSM177920 2 Negative Positive 3 34 GSM177920 4.73463 4.81658 4.78780 5.07658 6.39916 5.73216GSM177921 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM177921 4.5 Negative Positive 2 30 GSM177921 6.03832 5.51954 7.05546 6.10719 5.64183 4.99256GSM177922 Luminal B Luminal B Luminal A Luminal A Luminal A Luminal A GSM177922 3 Negative Positive 2 35 GSM177922 5.59927 3.86114 6.35652 5.40027 5.59197 3.73475GSM177923 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM177923 2.6 Negative Negative 3 56 GSM177923 4.08001 3.87940 5.16196 5.56509 6.35720 5.85760GSM177924 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM177924 3.2 Negative Negative 2 35 GSM177924 5.98443 5.39116 6.08974 5.96111 5.15858 4.90115GSM177925 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM177925 2.7 Negative Negative 3 52 GSM177925 4.04304 2.00494 3.78880 5.43627 6.52294 6.45327GSM177926 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B GSM177926 3 Negative Positive 3 47 GSM177926 6.31619 5.28279 6.04008 5.92421 6.55193 6.20672GSM177927 HER2 HER2 HER2 UC Luminal B Luminal B GSM177927 1.6 Negative Negative 3 42 GSM177927 4.05035 1.29753 8.30549 8.10030 6.64428 5.51137GSM177928 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM177928 1.7 Negative Positive 2 54 GSM177928 5.02295 2.48162 5.93493 4.95196 5.84231 4.70293GSM177929 Luminal B Luminal B HER2 UC Luminal B Luminal B GSM177929 2.5 Negative Positive 3 42 GSM177929 4.23440 3.63442 5.56714 5.68392 6.71314 5.38803GSM177930 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM177930 2.5 Negative Positive 2 50 GSM177930 5.74934 4.33989 6.17396 5.85489 4.63920 4.74290GSM177931 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM177931 3 Negative Positive 1 42 GSM177931 4.87469 5.30388 5.93824 5.84023 5.67500 3.51317GSM177932 Luminal B UC Luminal A Luminal A Luminal A Luminal A GSM177932 3.5 Negative Positive 1 38 GSM177932 5.37681 2.44019 5.84811 5.53201 6.75071 4.83206GSM177933 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B GSM177933 2.5 Negative Positive 3 37 GSM177933 4.97561 4.16490 6.07367 5.57022 7.87583 4.30063GSM177934 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM177934 3 Negative Positive 3 44 GSM177934 5.86809 4.57163 8.41402 7.59744 6.76326 5.72565GSM177935 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM177935 3.1 Negative Negative 3 37 GSM177935 3.73663 1.13262 5.63479 5.94083 6.43284 5.85849GSM177936 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM177936 1.5 Negative Positive 2 51 GSM177936 4.96202 4.54355 5.45767 5.38079 5.82035 4.51025GSM177937 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM177937 4 Negative Negative 3 53 GSM177937 3.34888 1.24406 5.81659 5.46908 6.35363 6.45946GSM177938 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM177938 2.5 Negative Positive 1 49 GSM177938 6.10683 2.75478 6.39230 5.75422 5.29626 4.84629GSM177939 Luminal B Luminal B HER2 HER2 HER2 HER2 GSM177939 3 Negative Negative 3 43 GSM177939 4.04653 1.82579 8.57897 7.20291 6.11672 5.72342GSM177940 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM177940 2.2 Negative Positive 2 39 GSM177940 5.84449 4.76078 5.96904 4.95898 6.14067 4.76622GSM177941 Luminal B Luminal B Luminal A Luminal A Luminal A Luminal A GSM177941 2 Negative Positive 2 47 GSM177941 5.77866 3.59433 5.27150 5.41118 5.77898 3.96712GSM177942 Luminal B Luminal B HER2 UC Luminal B Luminal B GSM177942 1.9 Negative Positive 3 42 GSM177942 4.68428 4.10366 6.08790 5.62199 6.56111 5.10831GSM177943 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM177943 1.2 Negative Negative 2 39 GSM177943 3.87426 1.22691 4.99205 5.32114 6.29451 5.78528GSM177944 Luminal B Luminal B Basal-like UC Luminal B Luminal B GSM177944 3 Negative Positive 2 52 GSM177944 2.94574 0.50985 3.67199 4.47433 6.82732 6.35289GSM177945 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM177945 1.5 Negative Positive 2 50 GSM177945 5.47758 5.14759 5.83225 5.65171 6.21357 5.33924GSM177946 Luminal B Luminal B Luminal A UC Luminal B Luminal B GSM177946 2.2 Negative Positive 3 36 GSM177946 5.09910 3.44232 5.53515 5.59609 6.50580 6.47010GSM177947 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM177947 2.5 Negative Positive 2 45 GSM177947 4.17895 5.16324 5.55469 5.48430 6.12773 4.91443GSM177948 Luminal B UC Luminal A Luminal A Luminal A Luminal A GSM177948 1.7 Negative Positive 1 50 GSM177948 4.15750 4.12907 4.99692 4.98929 5.46297 4.38763GSM177949 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM177949 2.3 Negative Positive 3 39 GSM177949 5.04170 2.40933 5.75640 5.32010 6.14711 5.08851GSM177950 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM177950 3 Negative Positive 1 44 GSM177950 5.20995 4.99922 5.77905 5.47021 5.39106 4.36310GSM177951 Luminal B UC Luminal A Luminal A Luminal A Luminal A GSM177951 1.3 Negative Positive 1 50 GSM177951 4.45050 5.40791 5.28273 5.30447 4.73974 4.14353GSM177952 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM177952 1.8 Negative Positive 2 51 GSM177952 4.52644 5.11280 4.70483 5.10060 5.85971 3.86020GSM177953 Luminal A Luminal A Luminal B Luminal B Luminal B Luminal B GSM177953 2 Negative Positive 1 49 GSM177953 5.65077 3.84406 6.68305 6.12985 6.31811 5.17953GSM177954 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM177954 2 Negative Negative 2 37 GSM177954 4.10188 2.37055 5.56832 3.96177 6.80159 6.02251GSM177955 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM177955 1.8 Negative Positive 2 51 GSM177955 4.82356 5.72650 6.11594 5.98511 5.33430 4.56007GSM177956 Luminal B Luminal B Basal-like Basal-like Basal-like Basal-like GSM177956 2 Negative Negative 3 40 GSM177956 3.71128 2.22659 4.83286 4.87160 6.12940 5.82272GSM177957 Luminal B UC Luminal A Luminal A Luminal A Luminal A GSM177957 2 Negative Positive 1 44 GSM177957 5.05410 1.35385 4.71362 5.06399 5.33031 4.30200GSM177958 Luminal B Luminal B Luminal A UC Luminal B Luminal B GSM177958 2 Negative Positive 3 49 GSM177958 5.75423 4.47839 5.71229 5.91592 6.61107 5.42955GSM177959 Luminal B Luminal B HER2 UC Luminal B Luminal B GSM177959 1.5 Negative Positive 1 53 GSM177959 3.70174 2.26074 7.78869 7.26197 6.01203 5.05550GSM177960 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B GSM177960 2.9 Negative Positive 2 44 GSM177960 5.43891 1.89890 5.81493 4.85831 6.19244 5.88696GSM177961 Luminal B UC Luminal A Luminal A Normal breast-like Normal breast-like GSM177961 2.3 Negative Positive 2 48 GSM177961 4.83547 5.29884 5.89698 5.72701 5.39533 4.82339GSM177962 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM177962 2.5 Negative Positive 2 57 GSM177962 5.80104 6.79615 6.63833 6.22005 5.87530 5.08422GSM177963 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM177963 3 Negative Positive 3 45 GSM177963 3.31216 1.91858 4.15969 4.99322 6.38964 4.85200GSM177964 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM177964 2 Negative Positive 1 44 GSM177964 4.93510 5.94421 6.37140 5.99838 5.48568 4.63301GSM177965 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM177965 1.5 Negative Positive 2 39 GSM177965 5.87034 6.19195 5.85273 5.60247 5.61714 5.41149GSM177966 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM177966 3 Negative Negative 3 40 GSM177966 4.00761 2.03126 5.71220 5.62453 6.35796 5.61341GSM177967 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM177967 2 Negative Positive 3 38 GSM177967 4.14603 3.94176 5.96741 5.46307 5.40695 4.87534GSM177968 Luminal B Luminal B HER2 UC Basal-like Basal-like GSM177968 2.6 Negative Positive 1 45 GSM177968 4.36890 2.10065 7.58693 6.45524 6.47746 5.84040GSM177969 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM177969 2.6 Negative Positive 2 43 GSM177969 5.37661 5.31743 5.66791 4.96883 5.94255 5.12278GSM177970 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM177970 1.5 Negative Negative 3 47 GSM177970 4.15420 2.21922 6.10926 5.34414 6.48490 6.03731GSM177971 Luminal B Luminal B Luminal A UC Luminal B Luminal B GSM177971 1.8 Negative Negative 2 38 GSM177971 5.50982 6.33283 4.95257 4.61329 6.47970 5.41139GSM177972 Luminal B UC Luminal A Luminal A Normal breast-like Normal breast-like GSM177972 2 Negative Negative 2 43 GSM177972 4.31838 4.50402 7.08674 7.13774 5.37489 5.32807GSM177973 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM177973 3.1 Negative Positive 3 60 GSM177973 4.90149 4.30777 4.56028 5.24276 6.95534 5.80216GSM177974 Luminal B Luminal B Luminal A UC Luminal B UC GSM177974 2 Negative Positive 2 42 GSM177974 4.05628 3.80207 7.10601 7.29767 6.36833 5.48937GSM177975 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM177975 2.1 Negative Negative 3 46 GSM177975 3.50213 3.33231 5.86212 5.58442 6.84568 5.97181GSM177976 Luminal A UC Luminal A Luminal A Normal breast-like Normal breast-like GSM177976 1 Negative Negative 2 47 GSM177976 4.31889 4.66118 4.49588 5.81156 6.14592 5.29324GSM177977 Luminal B Luminal B HER2 HER2 HER2 HER2 GSM177977 1 Negative Negative 3 54 GSM177977 3.63582 4.20727 7.35682 7.45628 6.89334 6.27898GSM177978 Luminal B Luminal B Basal-like Basal-like Basal-like Basal-like GSM177978 2.2 Negative Negative 3 47 GSM177978 4.38486 1.89679 5.04571 5.72463 6.87001 6.33835GSM177979 Luminal B Luminal B Basal-like Basal-like Basal-like Basal-like GSM177979 5 Negative Negative 3 39 GSM177979 3.62905 2.16330 4.66696 4.74205 6.63105 5.88450GSM177980 Luminal B Luminal B Basal-like UC Basal-like Basal-like GSM177980 3 Negative Negative 3 32 GSM177980 3.83167 2.83725 4.00970 5.48066 6.62527 7.08541GSM177981 Luminal B Luminal B HER2 HER2 HER2 HER2 GSM177981 2.5 Negative Negative 3 57 GSM177981 4.43988 2.61130 8.84530 8.95874 6.28313 6.11951GSM177982 Luminal B UC Luminal A Luminal A Luminal A Luminal A GSM177982 3.8 Negative Negative 2 47 GSM177982 4.56572 3.46141 5.65545 5.68582 5.71187 4.87121GSM177983 Luminal B UC Luminal A Luminal A Luminal B Luminal B GSM177983 1.8 Negative Positive 2 54 GSM177983 6.23053 6.47617 5.83241 5.59559 6.59827 5.71519GSM177984 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM177984 1.8 Negative Positive 1 54 GSM177984 4.20026 6.29331 5.92589 6.25759 4.86208 3.59846GSM177985 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM177985 4 Negative Negative 3 45 GSM177985 3.92392 0.87936 7.16407 6.75391 6.76298 5.68698GSM177986 Luminal B Luminal B HER2 HER2 Luminal B Luminal B GSM177986 2.2 Negative Positive 3 43 GSM177986 4.00923 1.97365 7.49099 7.10455 6.39019 5.78819GSM177987 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM177987 1 Negative Positive 1 48 GSM177987 6.35258 5.71576 6.40691 5.56999 4.87215 4.68850GSM177988 Luminal B Luminal B Basal-like UC Luminal B Luminal B GSM177988 2 Negative Positive 3 43 GSM177988 3.44008 1.50742 4.64235 4.87149 6.53839 5.78559GSM177989 Luminal B UC Luminal A Luminal A Luminal A Luminal A GSM177989 2 Negative Positive 2 43 GSM177989 5.08036 6.39266 6.36709 6.05272 5.62024 5.36772GSM177990 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM177990 0.8 Negative Positive 1 50 GSM177990 4.69901 5.23028 4.83515 5.69757 5.36115 5.43165GSM177991 Normal breast-like UC Luminal A Luminal A Normal breast-like Normal breast-like GSM177991 0.8 Negative Positive 1 43 GSM177991 4.03864 4.22766 4.55133 5.86133 5.05804 4.53926GSM177992 Luminal B UC Luminal A Luminal A Luminal A Luminal A GSM177992 1.3 Negative Positive 2 49 GSM177992 5.24180 5.97865 5.97634 5.57029 5.79484 5.11092GSM177993 Basal-like Basal-like Basal-like UC Basal-like Basal-like GSM177993 2 Negative Negative 2 38 GSM177993 3.46088 1.87496 5.60030 5.53611 5.51921 5.58202GSM177994 Basal-like Basal-like Basal-like UC Basal-like Basal-like GSM177994 0.9 Negative Negative 2 47 GSM177994 4.06249 2.33046 4.38910 5.08103 5.56305 5.46803GSM177995 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM177995 1 Negative Positive 2 54 GSM177995 6.87640 1.71020 6.81544 5.42071 6.01612 5.33279

Supplementary Table 7: Molecular subtype assignment of 198 breast cancers (‘TransBig’) 10 using the single sample predictors by Sorlie et al4, Hu et al5 and Parker et al6 using HUGO gene symbol for probe mapping and averaging of multiple probes identified to match a gene in a centroid/SSP; and ER status, age, histological grade, tumour size, lymph node status, and microarray-based mRNA expression levels of ESR1 , PGR , ERBB2 , GRB7 , AURKA and MKI67 .

17

GSM177996 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM177996 1.9 Negative Positive 1 52 GSM177996 5.70028 5.46804 6.58706 6.00843 4.92898 4.52096GSM177997 Luminal B UC Luminal A Luminal A Luminal B Luminal B GSM177997 1.4 Negative Positive 2 51 GSM177997 5.54961 5.46962 5.57771 4.91458 5.77168 5.16646GSM177998 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM177998 0.9 Negative Positive 2 50 GSM177998 5.83734 4.53890 6.28135 5.37904 5.78331 5.27299GSM177999 Basal-like Basal-like Basal-like UC Basal-like Basal-like GSM177999 4 Negative Negative 2 43 GSM177999 3.80422 2.15612 5.48679 5.79758 5.37811 5.89748GSM178000 Luminal B UC Luminal A Luminal A Luminal A Luminal A GSM178000 0.9 Negative Positive 2 24 GSM178000 4.38643 5.15427 5.92883 5.11685 6.39640 5.50344GSM178001 Basal-like Basal-like Basal-like UC Basal-like Basal-like GSM178001 1.4 Negative Positive 3 40 GSM178001 3.59082 4.22412 5.37638 5.36446 6.59032 5.90350GSM178002 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM178002 1 Negative Positive 2 56 GSM178002 5.60143 5.80060 5.95072 5.33046 5.26254 5.07515GSM178003 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM178003 2 Negative Negative 3 43 GSM178003 4.18520 1.04068 5.33268 5.66966 6.41760 5.57462GSM178004 Luminal B UC Luminal A Luminal A Luminal B Luminal B GSM178004 1.1 Negative Positive NA 50 GSM178004 5.00317 4.83792 8.02078 7.85261 5.23800 5.48425GSM178005 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM178005 1 Negative Positive 1 54 GSM178005 5.10104 4.79389 5.49400 5.59534 6.45407 5.38323GSM178006 HER2 HER2 HER2 HER2 HER2 HER2 GSM178006 2.2 Negative Negative 3 45 GSM178006 3.15672 1.74394 7.95994 7.58641 6.74198 5.58211GSM178007 Luminal B UC Luminal A Luminal A Luminal B Luminal B GSM178007 1.2 Negative Positive 2 43 GSM178007 4.46087 5.16183 5.30627 5.02871 5.26785 5.22149GSM178008 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM178008 2 Negative Positive 1 49 GSM178008 6.00405 5.26863 6.39237 5.82731 6.03318 5.72613GSM178009 HER2 HER2 HER2 UC Basal-like Basal-like GSM178009 3.8 Negative Negative 3 53 GSM178009 3.49936 2.08349 5.82130 5.35322 6.01361 5.76999GSM178010 HER2 HER2 HER2 HER2 HER2 HER2 GSM178010 1.1 Negative Negative 3 39 GSM178010 3.49775 3.79375 7.81746 7.38491 6.55173 5.82449GSM178011 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM178011 2.2 Negative Positive NA 38 GSM178011 4.39110 3.58210 5.33782 5.47443 6.02389 5.81802GSM178012 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM178012 2 Negative Positive 3 38 GSM178012 3.97090 0.61361 5.94855 5.59913 6.84625 6.27670GSM178013 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM178013 1.2 Negative Negative 3 40 GSM178013 3.71750 2.13804 5.17753 5.19125 7.12100 6.40764GSM178014 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM178014 1.5 Negative Positive 2 38 GSM178014 5.03775 6.02495 5.49453 4.76906 5.80575 5.71376GSM178015 HER2 UC Luminal A Luminal A Luminal A Luminal A GSM178015 1.7 Negative Positive 2 54 GSM178015 4.93967 3.97916 8.23356 7.09501 5.35476 4.71008GSM178016 Luminal B UC Luminal A Luminal A Luminal A Luminal A GSM178016 2.1 Negative Positive 2 40 GSM178016 4.32137 2.22103 5.47526 5.06626 5.32278 5.02845GSM178017 HER2 UC HER2 UC Luminal B Luminal B GSM178017 1 Negative Negative 3 56 GSM178017 3.50487 3.53555 4.88627 5.00245 6.32224 5.77732GSM178018 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM178018 2 Negative Positive 2 45 GSM178018 5.81868 3.99911 5.99442 5.85764 6.10223 5.64575GSM178019 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM178019 2 Negative Positive 2 46 GSM178019 5.17262 5.40730 5.75960 4.48886 5.50932 4.61598GSM178020 Luminal B Luminal B HER2 UC Luminal B Luminal B GSM178020 1.6 Negative Positive 3 45 GSM178020 4.31834 4.53118 6.89810 6.46079 6.97080 5.75357GSM178021 Luminal B Luminal B Basal-like Basal-like Basal-like Basal-like GSM178021 2.8 Negative Negative 3 33 GSM178021 4.27242 2.12826 4.74880 4.83050 6.45680 5.84443GSM178022 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM178022 2.4 Negative Negative 3 37 GSM178022 5.01650 5.43198 5.15435 3.83832 5.71232 5.23158GSM178023 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM178023 2.5 Negative Negative 3 42 GSM178023 4.15174 1.60815 4.83046 5.67400 7.17272 6.44425GSM178024 Normal breast-like UC Luminal A Luminal A Normal breast-like Normal breast-like GSM178024 1.1 Negative Positive 3 47 GSM178024 4.15395 6.32572 6.12892 5.44471 5.20170 4.23562GSM178025 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B GSM178025 2 Negative Positive 2 43 GSM178025 4.59895 5.00928 6.13088 5.21679 7.05666 5.83342GSM178026 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM178026 1.6 Negative Positive 3 44 GSM178026 5.50761 4.28822 4.81977 5.44562 6.04397 5.56536GSM178027 Luminal B UC Luminal A Luminal A Luminal A Luminal A GSM178027 2.3 Negative Positive 2 54 GSM178027 5.04815 4.67258 5.78474 5.28841 5.84536 5.41373GSM178028 HER2 HER2 HER2 UC HER2 HER2 GSM178028 1.8 Negative Negative 2 51 GSM178028 3.63521 0.68470 8.00592 8.02083 6.44589 5.87839GSM178029 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM178029 2 Negative Positive 2 42 GSM178029 5.02148 4.18669 5.74316 5.46210 5.30039 4.95633GSM178030 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM178030 2.2 Negative Positive 2 56 GSM178030 5.80005 3.90595 5.55326 5.10722 5.58884 5.40486GSM178031 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM178031 2.5 Negative Positive 2 56 GSM178031 6.39980 5.90929 5.92081 5.58263 5.91038 5.55527GSM178032 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM178032 2.3 Negative Positive 3 58 GSM178032 4.96449 4.67563 5.84810 5.16852 4.83993 4.11181GSM178033 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM178033 2.2 Negative Positive 2 58 GSM178033 4.99395 3.88598 5.91157 5.07707 4.23139 3.98257GSM178034 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM178034 1.5 Negative Positive 2 32 GSM178034 3.35350 0.98236 5.16926 4.82501 6.96993 6.84109GSM178035 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM178035 1.9 Negative Positive 3 50 GSM178035 4.23191 0.89380 4.75682 5.92190 6.21355 5.88782GSM178036 Luminal A UC Luminal A Luminal A Luminal B Luminal B GSM178036 1.3 Negative Negative 3 49 GSM178036 5.74317 5.43746 7.41368 7.05210 5.40117 5.51601GSM178037 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM178037 1.9 Negative Positive 1 47 GSM178037 4.93859 5.63269 6.19758 5.16589 5.58380 5.10510GSM178038 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM178038 2.2 Negative Positive 2 56 GSM178038 6.72742 1.89681 6.29007 5.99676 6.35901 5.69288GSM178039 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM178039 1 Negative Positive 1 55 GSM178039 5.10838 1.23742 6.38048 5.68447 4.79651 4.12226GSM178040 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM178040 1.8 Negative Positive 2 48 GSM178040 4.80848 5.27104 6.00303 5.22768 5.30042 5.39278GSM178041 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM178041 0.9 Negative Positive 2 56 GSM178041 5.49586 6.32737 5.35110 5.06316 5.23481 5.07774GSM178042 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM178042 2 Negative Positive 2 51 GSM178042 5.69211 5.45701 5.10901 4.99772 5.48454 4.89687GSM178043 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM178043 1.2 Negative Positive 3 44 GSM178043 4.67208 4.47490 5.46243 5.38351 5.12961 4.82352GSM178044 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM178044 1.2 Negative Negative 2 46 GSM178044 4.97622 5.33662 5.85145 5.80622 5.79157 5.33945GSM178045 Luminal B UC Luminal A Luminal A Luminal A Luminal A GSM178045 1.2 Negative Positive 1 36 GSM178045 4.95274 4.25726 5.83191 5.10133 5.69119 5.29662GSM178046 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM178046 1.3 Negative Positive 2 44 GSM178046 4.49049 6.28708 5.87562 5.05196 6.03292 5.03492GSM178047 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM178047 2.2 Negative Positive 2 41 GSM178047 5.61207 5.22957 6.80141 6.19163 5.60856 5.13023GSM178048 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM178048 3 Negative Positive 2 60 GSM178048 7.04672 5.20770 5.77724 5.70322 5.58607 5.21549GSM178049 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM178049 3 Negative Positive 2 59 GSM178049 6.95839 6.11635 6.14542 5.39786 7.04498 5.51976GSM178050 Luminal B Luminal B HER2 HER2 Luminal B Luminal B GSM178050 2.7 Negative Negative 3 48 GSM178050 5.45585 1.22768 7.27387 6.93989 7.50153 5.59494GSM178051 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM178051 3 Negative Positive 2 53 GSM178051 5.99161 4.57948 6.04436 5.63348 5.18301 5.28847GSM178052 Luminal B Luminal B HER2 HER2 Luminal B Luminal B GSM178052 4 Negative Negative 3 43 GSM178052 3.91321 2.25491 8.24118 8.32589 6.41350 6.30593GSM178053 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM178053 1.5 Negative Positive 2 33 GSM178053 4.91736 1.58127 6.11832 5.26250 5.86600 5.39866GSM178054 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM178054 2.6 Negative Positive 1 42 GSM178054 5.08563 6.00535 5.97964 5.35098 4.73725 4.29025GSM178055 Luminal B Luminal B HER2 UC Luminal B Luminal B GSM178055 4 Negative Negative 3 51 GSM178055 3.42292 3.16730 3.32887 4.08429 6.74695 6.62314GSM178056 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM178056 1.7 Negative Positive 3 31 GSM178056 5.55318 5.28139 6.05077 5.38000 6.32892 4.99377GSM178057 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM178057 3.2 Negative Positive 3 60 GSM178057 6.03940 5.52242 3.53522 4.87131 5.97371 4.75094GSM178058 Luminal B Luminal B HER2 UC Luminal B Luminal B GSM178058 2 Negative Positive 3 46 GSM178058 4.17121 1.03617 6.19949 5.72984 6.85901 4.97414GSM178059 Luminal B Luminal B Basal-like UC Basal-like Basal-like GSM178059 2.1 Negative Negative 3 59 GSM178059 3.52553 4.00618 5.64930 4.74440 6.74152 5.64131GSM178060 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B GSM178060 3.2 Negative Positive 1 24 GSM178060 4.96537 1.64783 6.01549 5.03016 6.64629 5.37227GSM178061 Luminal B UC Luminal A Luminal A Luminal A Luminal A GSM178061 3 Negative Positive 2 54 GSM178061 6.03297 1.21988 5.79631 5.75099 6.63278 4.02826GSM178062 Luminal B UC Luminal A UC Normal breast-like UC GSM178062 0.8 Negative Positive 2 55 GSM178062 5.03035 3.27309 5.67368 5.29209 5.89779 5.08234GSM178063 Luminal B Luminal B HER2 HER2 HER2 HER2 GSM178063 2.1 Negative Negative 3 41 GSM178063 2.98453 3.68050 7.84799 7.57330 6.87278 5.61171GSM178064 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM178064 2.5 Negative Positive 3 42 GSM178064 6.27652 4.78667 5.82510 5.37332 6.10629 5.86405GSM178065 Luminal B Luminal B HER2 UC Luminal B Luminal B GSM178065 2.5 Negative Negative 3 47 GSM178065 4.27503 1.70345 7.42354 6.79456 6.12163 6.06497GSM178066 Luminal B Luminal B HER2 HER2 HER2 HER2 GSM178066 2.2 Negative Negative 3 53 GSM178066 3.68147 1.70438 8.64281 8.66156 6.79499 5.68824GSM178067 Luminal A UC Luminal A Luminal A Luminal A Luminal A GSM178067 2.4 Negative Positive 2 50 GSM178067 5.42828 5.63022 6.55808 5.58856 5.34511 5.36877GSM178068 Luminal B Luminal B Luminal B Luminal B Luminal B Luminal B GSM178068 2.2 Negative Positive 3 44 GSM178068 5.56420 3.74765 5.85120 5.31339 6.93482 5.75252GSM178069 Luminal B Luminal B Luminal A UC Luminal B Luminal B GSM178069 1.5 Negative Negative 1 48 GSM178069 6.91208 2.29759 5.23312 5.47690 6.38297 6.09887GSM178070 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM178070 3 Negative Positive 2 49 GSM178070 5.83075 5.40469 6.24169 5.28988 5.27537 4.75448GSM178071 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM178071 2.5 Negative Positive 2 43 GSM178071 5.21518 2.83793 6.11730 5.49214 5.88488 4.59222GSM178072 Luminal A Luminal A Luminal A Luminal A Luminal A Luminal A GSM178072 2 Negative Positive 1 45 GSM178072 5.13178 6.08869 5.57526 4.84159 5.99639 5.08919GSM178073 HER2 HER2 HER2 HER2 HER2 HER2 GSM178073 1.4 Negative Negative 3 53 GSM178073 3.54847 1.50501 8.66189 7.79344 7.13734 6.00878GSM178074 Luminal B Luminal B Luminal A Luminal A Luminal B Luminal B GSM178074 4.2 Negative Positive 3 40 GSM178074 5.03572 0.88598 5.71090 5.60655 6.16111 5.64523GSM178075 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM178075 3.2 Negative Negative 3 48 GSM178075 4.01348 2.52094 5.37139 5.22926 7.38525 5.78037GSM178076 Luminal B UC Luminal A Luminal A Luminal A Luminal A GSM178076 1.5 Negative Positive 2 56 GSM178076 5.32523 5.05027 5.70870 5.07241 5.75736 4.94529GSM178077 Luminal B UC Luminal A Luminal A Luminal A Luminal A GSM178077 1.7 Negative Positive 2 45 GSM178077 5.25212 5.02533 5.21430 5.16732 5.91106 5.00029GSM178078 Basal-like Basal-like Basal-like Basal-like Basal-like Basal-like GSM178078 2.2 Negative Negative 3 39 GSM178078 3.80004 2.18686 5.68579 5.60194 6.48950 5.42087GSM178079 Luminal B Luminal B Basal-like Basal-like Basal-like Basal-like GSM178079 3.2 Negative Negative 3 46 GSM178079 3.80645 1.08167 5.64101 6.23653 7.03150 5.53739GSM178080 Luminal A Luminal A Luminal A Luminal A Luminal B Luminal B GSM178080 2.5 Negative Positive 1 47 GSM178080 6.16113 5.70986 4.17888 5.66257 6.17951 5.65197GSM178081 Luminal B Luminal B Luminal A Luminal A Luminal A Luminal A GSM178081 1.2 Negative Positive 2 43 GSM178081 4.87995 4.63604 6.42531 6.04760 5.64839 5.14438GSM178082 Luminal B Luminal B Basal-like Basal-like Basal-like Basal-like GSM178082 2.5 Negative Negative 3 39 GSM178082 3.34745 1.20710 5.48336 5.20353 6.53834 5.58084


18

SSP Sorlie 2003 Kappa score 95% Confidence intervalsBasal-like Luminal A Luminal B Normal breast-like HER2 Unclassified 0.303 0.183 - 0.423

Basal-like 12 0 0 0 0 0Luminal A 0 6 6 0 0 2

SSP Hu 2006 Luminal B 0 0 0 0 0 0Normal breast-like 0 0 0 0 0 0HER2 0 0 0 0 0 0Unclassified 1 0 23 0 0 3

SSP Sorlie 2003 0.668 0.500 - 0.837Basal-like 13 0 0 0 0 0Luminal A 0 1 0 0 0 2

SSP Parker 2009 Luminal B 0 5 28 0 0 2Normal breast-like 0 0 0 0 0 0HER2 0 0 0 0 0 0Unclassified 0 0 1 0 0 1

SSP Parker 2009 0.254 0.157 - 0.351Basal-like 12 0 0 0 0 0Luminal A 0 3 11 0 0 0























Supplementary Table 8: Results of Kappa score analysis (and 95% confidence intervals) to determine agreement between molecular subtype assignments made using three different single sample predictors4-6 of breast cancers from four cohorts (53 grade III IDCs, ‘NKI-295’ 8, ‘Wang’9 and ‘TransBig’10 datasets). A: All cases, including unclassified cases with cut-off correlation to any subtype <0.1; B: Exclusion of unclassified cases with correlation <0.1 to any centroid/SSP. SSP: single sample predictor.

53 GIII IDC dataset

NKI-295 dataset

Wang dataset

TransBig dataset

A: All cases, including unclassified cases with cut-off correlation to any subtype <0.1

19

SSP Sorlie 2003 Kappa score 95% Confidence intervalsBasal-like Luminal A Luminal B Normal breast-like HER2 0.600 0.395 - 0.805

Basal-like 12 0 0 0 0Luminal A 0 6 6 0 0

SSP Hu 2006 Luminal B 0 0 0 0 0Normal breast-like 0 0 0 0 0HER2 0 0 0 0 0

SSP Sorlie 2003 0.788 0.623 - 0.953Basal-like 13 0 0 0 0Luminal A 0 1 0 0 0

SSP Parker 2009 Luminal B 0 5 28 0 0Normal breast-like 0 0 0 0 0HER2 0 0 0 0 0

SSP Parker 2009Basal-like 12 0 0 0 0 0.416 0.267 - 0.565

SSP Hu 2006 Luminal A 0 3 11 0 0Luminal B 0 0 0 0 0Normal breast-like 0 0 0 0 0HER2 0 0 0 0 0






SSP Parker 2009 0.693 0.627 - 0.758Basal-like 45 0 2 0 6
















B: Exclusion of unclassified cases with correlation <0.1 to any subtype

TransBig dataset

53 GIII IDC dataset

NKI-295 dataset

Wang dataset

20

Molecular SubtypeKappa Score 95% CI Kappa Score 95% CI Kappa Score 95% CI

Basal-like 0.948 0.846 – 1.049 1 1.000 – 1.000 0.948 0.846 – 1.049HER2 NA NA NA NA NA NALuminal A 0.525 0.258 – 0.792 0.159 -0.215 – 0.532 0.286 0.023 – 0.549Luminal B NA NA 0.689 0.496 – 0.882 NA NANormal breast-like NA NA NA NA NA NA

Kappa Score 95% CI Kappa Score 95% CI Kappa Score 95% CIBasal-like 0.891 0.821 – 0.961 0.962 0.919 – 1.005 0.88 0.807 – 0.953HER2 0.536 0.388 – 0.685 0.615 0.491 – 0.740 0.687 0.570 – 0.804Luminal A 0.406 0.308 – 0.505 0.371 0.254 – 0.487 0.641 0.554 – 0.728Luminal B 0.322 0.182 – 0.461 0.296 0.173 – 0.420 0.558 0.445 – 0.670Normal breast-like 0.376 0.160 – 0.592 0.316 0.117 – 0.516 0.474 0.282 – 0.665

Kappa Score 95% CI Kappa Score 95% CI Kappa Score 95% CIBasal-like 0.961 0.918 – 1.005 0.902 0.835 – 0.969 0.939 0.886 – 0.992HER2 0.258 0.040 – 0.477 0.248 0.001 – 0.495 0.704 0.531 – 0.877Luminal A 0.529 0.443 – 0.616 0.253 0.132 – 0.274 0.372 0.290 – 0.455Luminal B 0.191 0.104 – 0.278 0.364 0.259 – 0.468 0.127 0.069 – 0.185Normal breast-like NA NA NA NA NA NA

Kappa Score 95% CI Kappa Score 95% CI Kappa Score 95% CIBasal-like 0.787 0.666 – 0.908 0.812 0.706 – 0.918 0.831 0.730- 0.932HER2 0.331 0.070 – 0.593 0.535 0.252 – 0.819 0.753 0.564 – 0.942Luminal A 0.344 0.248 – 0.441 0.212 0.069 – 0.354 0.544 0.442 – 0.645Luminal B 0.148 0.047 – 0.249 0.423 0.291 – 0.554 0.151 0.060 – 0.241Normal breast-like NA NA NA NA NA NA

Supplementary Table 9: Agreement between three single sample predictors (SSPs), using a correlation cut-off of <0.1 to each subtype, for the classification of each molecular subtype separately in four cohorts of breast cancers (53 grade III IDCs, ‘NKI-295’8, ‘Wang’9 and ‘TransBig’10

datasets). 53 GIII IDC dataset - Kappa scores

Sorlie 2003 vs Hu 2006, cut-off <0.1 Sorlie 2003 vs Parker 2009, cut-off <0.1 Hu 2006 vs Parker 2009, cut-off <0.1

NKI-295 dataset - Kappa scores


NA: not applicable. 95% CI: 95% confidence intervals.

Wang dataset - Kappa scores


TransBig dataset - Kappa scores


21

Lower UpperLymph node (Positive vs negative) -0.116 0.206 0.32 1 0.572 0.89 0.595 1.332GRADE (1 vs 2 vs 3) 5.764 2 0.056GRADE 2 vs 1 0.651 0.357 3.317 1 0.069 1.917 0.952 3.861GRADE 3 vs 1 0.892 0.372 5.759 1 0.016 2.441 1.178 5.059ER (Positive vs Negative) -0.254 0.329 0.595 1 0.441 0.776 0.407 1.479TUMOUR SIZE 0.028 0.011 6.575 1 0.01 1.029 1.007 1.052SSP Sorlie Overall 8.782 4 0.067SSP Sorlie (Luminal A vs basal-like) -0.28 0.462 0.367 1 0.545 0.756 0.306 1.869SSP Sorlie (Luminal B vs basal-like) 0.356 0.4 0.789 1 0.374 1.427 0.651 3.127SSP Sorlie (Normal breast-like vs basal-like) -0.271 0.56 0.235 1 0.628 0.762 0.255 2.283SSP Sorlie (HER2 vs basal-like) 0.534 0.363 2.158 1 0.142 1.705 0.837 3.474

Lower UpperLymph node (Positive vs negative) -0.205 0.211 0.942 1 0.332 0.815 0.538 1.233GRADE (1 vs 2 vs 3) 6.826 2 0.033GRADE 2 vs 1 0.643 0.354 3.293 1 0.07 1.902 0.95 3.81GRADE 3 vs 1 0.952 0.366 6.751 1 0.009 2.591 1.264 5.314ER (Positive vs Negative) -0.341 0.35 0.948 1 0.33 0.711 0.358 1.412TUMOUR SIZE 0.031 0.012 7.054 1 0.008 1.031 1.008 1.055SSP Hu Overall 25.016 4 <0.001SSP Hu (Luminal A vs basal-like) -0.453 0.442 1.053 1 0.305 0.636 0.268 1.51SSP Hu (Luminal B vs basal-like) 0.912 0.417 4.796 1 0.029 2.491 1.101 5.636SSP Hu (Normal breast-like vs basal-like) 0.731 0.463 2.487 1 0.115 2.076 0.838 5.147SSP Hu (HER2 vs basal-like) 0.281 0.346 0.657 1 0.418 1.324 0.672 2.609

Lower UpperLymph node (Positive vs negative) -0.232 0.207 1.256 1 0.262 0.793 0.529 1.189GRADE (1 vs 2 vs 3) 3.654 2 0.161GRADE 2 vs 1 0.505 0.358 1.989 1 0.158 1.657 0.821 3.343GRADE 3 vs 1 0.698 0.366 3.639 1 0.056 2.009 0.981 4.114ER (Positive vs Negative) -0.27 0.359 0.567 1 0.452 0.763 0.378 1.542TUMOUR SIZE 0.031 0.012 6.974 1 0.008 1.031 1.008 1.055SSP Parker Overall 17.631 4 0.001SSP Parker (Luminal A vs basal-like) -0.683 0.515 1.76 1 0.185 0.505 0.184 1.386SSP Parker (Luminal B vs basal-like) 0.553 0.447 1.53 1 0.216 1.738 0.724 4.171SSP Parker (Normal breast-like vs basal-like) -0.306 0.57 0.289 1 0.591 0.736 0.241 2.251SSP Parker (HER2 vs basal-like) 0.529 0.348 2.303 1 0.129 1.697 0.857 3.358

Lower UpperLymph node (Positive vs negative) -0.097 0.207 0.219 1 0.64 0.908 0.605 1.362GRADE (1 vs 2 vs 3) 7.253 2 0.027GRADE 2 vs 1 0.757 0.355 4.545 1 0.033 2.133 1.063 4.278GRADE 3 vs 1 1.025 0.381 7.233 1 0.007 2.787 1.321 5.882ER (Positive vs Negative) -0.391 0.343 1.301 1 0.254 0.676 0.345 1.324TUMOUR SIZE 0.025 0.011 5.427 1 0.02 1.026 1.004 1.048SSP Sorlie cut-off <0.1 Overall 3.83 5 0.574SSP Sorlie (Luminal A vs basal-like) 0.152 0.495 0.094 1 0.759 1.164 0.441 3.068SSP Sorlie (Luminal B vs basal-like) 0.507 0.412 1.513 1 0.219 1.66 0.74 3.721SSP Sorlie (Normal breast-like vs basal-like) -0.121 0.704 0.029 1 0.864 0.886 0.223 3.522SSP Sorlie (HER2 vs basal-like) 0.421 0.376 1.256 1 0.262 1.524 0.729 3.185SSP Sorlie (Unclassifiable vs basal-like) 0.092 0.465 0.039 1 0.843 1.096 0.441 2.728

Lower UpperLymph node (Positive vs negative) -0.16 0.21 0.575 1 0.448 0.852 0.564 1.288GRADE (1 vs 2 vs 3) 6.665 2 0.036GRADE 2 vs 1 0.623 0.355 3.081 1 0.079 1.865 0.93 3.741GRADE 3 vs 1 0.94 0.367 6.557 1 0.01 2.56 1.247 5.257ER (Positive vs Negative) -0.509 0.371 1.882 1 0.17 0.601 0.29 1.244TUMOUR SIZE 0.028 0.011 5.795 1 0.016 1.028 1.005 1.051SSP Hu cut-off <0.1 Overall 22.081 5 0.001SSP Hu (Luminal A vs basal-like) -0.243 0.48 0.257 1 0.612 0.784 0.306 2.008SSP Hu (Luminal B vs basal-like) 1.062 0.453 5.502 1 0.019 2.893 1.191 7.03SSP Hu (Normal breast-like vs basal-like) 0.753 0.5 2.268 1 0.132 2.124 0.797 5.663SSP Hu (HER2 vs basal-like) 0.289 0.375 0.594 1 0.441 1.335 0.64 2.785SSP Hu (Unclassifiable vs basal-like) 0.57 0.494 1.329 1 0.249 1.768 0.671 4.66

Lower UpperLymph node (Positive vs negative) -0.251 0.207 1.468 1 0.226 0.778 0.519 1.168GRADE (1 vs 2 vs 3) 3.07 2 0.215GRADE 2 vs 1 0.453 0.36 1.583 1 0.208 1.572 0.777 3.183GRADE 3 vs 1 0.636 0.365 3.039 1 0.081 1.889 0.924 3.863ER (Positive vs Negative) -0.332 0.367 0.819 1 0.366 0.718 0.35 1.472TUMOUR SIZE 0.033 0.012 7.646 1 0.006 1.033 1.01 1.058SSP Parker cut-off <0.1 Overall 20.842 5 0.001SSP Parker (Luminal A vs basal-like) -0.664 0.53 1.574 1 0.21 0.515 0.182 1.453SSP Parker (Luminal B vs basal-like) 0.667 0.458 2.114 1 0.146 1.948 0.793 4.784SSP Parker (Normal breast-like vs basal-like) -0.381 0.605 0.396 1 0.529 0.683 0.209 2.237SSP Parker (HER2 vs basal-like) 0.632 0.352 3.226 1 0.072 1.882 0.944 3.75SSP Parker (Unclassifiable vs basal-like) 0.8 0.723 1.226 1 0.268 2.226 0.54 9.175

Hazard Ratio

95.0% CI for Hazard Ratio

Supplementary Table 10: Multivariable Cox hazard analyses of the ‘NKI-295’ 8 and ‘TransBig’10 datasets including histological grade (categorical 1, 2 or 3), tumour size (continuous in mm), lymph node status (categorical positive vs negative), ER status (categorical positive vs negative) and breast cancer molecular subtypes assigned using three distinct single sample predictors (categorical) and association with overall or metastasis-free survival

Hazard Ratio

95.0% CI for Hazard RatioB SE Wald df P Value

B SE Wald

df P Value Hazard Ratio

95.0% CI for Hazard RatioB SE Wald

Hazard Ratio


B SE Wald df P Value Hazard Ratio


SSP Sorlie et al 2003

SSP Hu et al 2006

NKI-295 dataset

Metastasis-free survival

B SE Wald df P Value

SSP Parker et al 2009

SSP Sorlie et al 2003, including unclassified cases, cut-off <0.1



SSP Hu et al 2006, including unclassified cases, cut-off <0.1

SSP Parker et al 2009, including unclassified cases, cut-off <0.1


22

Lower UpperLymph node (Positive vs negative) -0.067 0.232 0.084 1 0.772 0.935 0.593 1.474GRADE (1 vs 2 vs 3) 7.416 2 0.025GRADE 2 vs 1 1.217 0.549 4.911 1 0.027 3.379 1.151 9.917GRADE 3 vs 1 1.506 0.557 7.314 1 0.007 4.511 1.514 13.44ER (Positive vs Negative) -0.485 0.366 1.76 1 0.185 0.616 0.301 1.26TUMOUR SIZE 0.024 0.013 3.535 1 0.06 1.024 0.999 1.05SSP Sorlie Overall 7.535 4 0.11SSP Sorlie (Luminal A vs basal-like) -0.875 0.535 2.676 1 0.102 0.417 0.146 1.189SSP Sorlie (Luminal B vs basal-like) -0.045 0.429 0.011 1 0.916 0.956 0.412 2.217SSP Sorlie (Normal breast-like vs basal-like) -0.888 0.703 1.593 1 0.207 0.412 0.104 1.634SSP Sorlie (HER2 vs basal-like) 0.187 0.364 0.263 1 0.608 1.205 0.591 2.458

Lower UpperLymph node (Positive vs negative) -0.105 0.236 0.199 1 0.656 0.9 0.567 1.429GRADE (1 vs 2 vs 3) 8.803 2 0.012GRADE 2 vs 1 1.263 0.547 5.323 1 0.021 3.535 1.209 10.334GRADE 3 vs 1 1.627 0.556 8.552 1 0.003 5.088 1.71 15.138ER (Positive vs Negative) -0.662 0.381 3.025 1 0.082 0.516 0.244 1.088TUMOUR SIZE 0.024 0.013 3.359 1 0.067 1.024 0.998 1.051SSP Hu Overall 8.74 4 0.068SSP Hu (Luminal A vs basal-like) -0.607 0.488 1.547 1 0.214 0.545 0.209 1.419SSP Hu (Luminal B vs basal-like) 0.451 0.465 0.942 1 0.332 1.57 0.631 3.908SSP Hu (Normal breast-like vs basal-like) 0.057 0.581 0.01 1 0.922 1.058 0.339 3.306SSP Hu (HER2 vs basal-like) 0.127 0.342 0.138 1 0.71 1.135 0.581 2.219

Lower UpperLymph node (Positive vs negative) -0.198 0.233 0.723 1 0.395 0.82 0.519 1.295GRADE (1 vs 2 vs 3) 4.496 2 0.106GRADE 2 vs 1 0.958 0.55 3.027 1 0.082 2.606 0.886 7.663GRADE 3 vs 1 1.155 0.548 4.443 1 0.035 3.175 1.084 9.298ER (Positive vs Negative) -0.34 0.385 0.779 1 0.378 0.712 0.334 1.515TUMOUR SIZE 0.028 0.014 4.273 1 0.039 1.029 1.001 1.057SSP Parker Overall 17.584 4 0.001SSP Parker (Luminal A vs basal-like) -1.975 0.68 8.442 1 0.004 0.139 0.037 0.526SSP Parker (Luminal B vs basal-like) -0.026 0.474 0.003 1 0.956 0.974 0.385 2.465SSP Parker (Normal breast-like vs basal-like) -1.499 0.821 3.334 1 0.068 0.223 0.045 1.116SSP Parker (HER2 vs basal-like) 0.179 0.345 0.271 1 0.603 1.196 0.609 2.351

Lower UpperLymph node (Positive vs negative) -0.065 0.233 0.076 1 0.782 0.937 0.593 1.482GRADE (1 vs 2 vs 3) 7.392 2 0.025GRADE 2 vs 1 1.283 0.548 5.486 1 0.019 3.608 1.233 10.559GRADE 3 vs 1 1.531 0.563 7.391 1 0.007 4.622 1.533 13.934ER (Positive vs Negative) -0.588 0.376 2.443 1 0.118 0.555 0.266 1.161TUMOUR SIZE 0.021 0.013 2.817 1 0.093 1.021 0.996 1.047SSP Sorlie cut-off <0.1 Overall 5.179 5 0.394SSP Sorlie (Luminal A vs basal-like) -0.598 0.576 1.078 1 0.299 0.55 0.178 1.701SSP Sorlie (Luminal B vs basal-like) 0.153 0.436 0.124 1 0.725 1.166 0.496 2.739SSP Sorlie (Normal breast-like vs basal-like) -1.202 1.084 1.23 1 0.267 0.301 0.036 2.514SSP Sorlie (HER2 vs basal-like) 0.102 0.374 0.074 1 0.785 1.107 0.532 2.306SSP Sorlie (Unclassifiable vs basal-like) -0.469 0.519 0.817 1 0.366 0.626 0.226 1.729

Lower UpperLymph node (Positive vs negative) -0.084 0.236 0.126 1 0.723 0.92 0.579 1.461GRADE (1 vs 2 vs 3) 8.611 2 0.013GRADE 2 vs 1 1.246 0.548 5.172 1 0.023 3.475 1.188 10.168GRADE 3 vs 1 1.61 0.557 8.359 1 0.004 5.002 1.68 14.899ER (Positive vs Negative) -0.747 0.403 3.435 1 0.064 0.474 0.215 1.044TUMOUR SIZE 0.022 0.013 2.757 1 0.097 1.022 0.996 1.049SSP Hu cut-off <0.1 Overall 8.203 5 0.145SSP Hu (Luminal A vs basal-like) -0.532 0.525 1.027 1 0.311 0.588 0.21 1.643SSP Hu (Luminal B vs basal-like) 0.523 0.496 1.111 1 0.292 1.686 0.638 4.455SSP Hu (Normal breast-like vs basal-like) -0.075 0.634 0.014 1 0.906 0.928 0.268 3.216SSP Hu (HER2 vs basal-like) 0.079 0.373 0.045 1 0.832 1.083 0.521 2.251SSP Hu (Unclassifiable vs basal-like) 0.102 0.541 0.036 1 0.85 1.107 0.383 3.199

Lower UpperLymph node (Positive vs negative) -0.208 0.233 0.792 1 0.374 0.812 0.514 1.284GRADE (1 vs 2 vs 3) 4.302 2 0.116GRADE 2 vs 1 0.901 0.552 2.661 1 0.103 2.462 0.834 7.269GRADE 3 vs 1 1.121 0.549 4.178 1 0.041 3.069 1.047 8.996ER (Positive vs Negative) -0.412 0.398 1.074 1 0.3 0.662 0.304 1.444TUMOUR SIZE 0.029 0.014 4.433 1 0.035 1.03 1.002 1.058SSP Parker cut-off <0.1 Overall 18.253 5 0.003SSP Parker (Luminal A vs basal-like) -1.845 0.688 7.196 1 0.007 0.158 0.041 0.608SSP Parker (Luminal B vs basal-like) 0.094 0.488 0.037 1 0.847 1.099 0.422 2.857SSP Parker (Normal breast-like vs basal-like) -2.068 1.088 3.617 1 0.057 0.126 0.015 1.065SSP Parker (HER2 vs basal-like) 0.277 0.347 0.64 1 0.424 1.32 0.669 2.603SSP Parker (Unclassifiable vs basal-like) 0.215 0.841 0.065 1 0.798 1.24 0.238 6.45

NKI-295 dataset

Overall survival



B SE Wald

B SE Wald

B SE Wald

Hazard Ratio





SSP Hu et al 2006



df P Value



Hazard Ratio


Hazard Ratio


Hazard Ratio



df P Value


23

Lower UpperGRADE (1 vs 2 vs 3) 2.812 2 0.245GRADE 2 vs 1 0.162 0.431 0.141 1 0.708 1.176 0.505 2.738GRADE 3 vs 1 -0.405 0.486 0.695 1 0.404 0.667 0.257 1.728ER (Positive vs Negative) -0.428 0.339 1.594 1 0.207 0.652 0.335 1.267TUMOUR SIZE 0.422 0.153 7.653 1 0.006 1.525 1.131 2.057SSP Sorlie Overall 7.366 4 0.118SSP Sorlie (Luminal A vs basal-like) -0.583 0.523 1.239 1 0.266 0.558 0.2 1.558SSP Sorlie (Luminal B vs basal-like) 0.141 0.415 0.116 1 0.734 1.152 0.51 2.599SSP Sorlie (Normal breast-like vs basal-like) -10.714 251.39 0.002 1 0.966 0 0 2.128729395363696+209SSP Sorlie (HER2 vs basal-like) 0.841 0.553 2.314 1 0.128 2.319 0.785 6.855

Lower UpperGRADE (1 vs 2 vs 3) 3.788 2 0.15GRADE 2 vs 1 0.261 0.432 0.364 1 0.546 1.298 0.556 3.029GRADE 3 vs 1 -0.48 0.505 0.903 1 0.342 0.619 0.23 1.665ER (Positive vs Negative) -0.799 0.385 4.299 1 0.038 0.45 0.211 0.957TUMOUR SIZE 0.322 0.152 4.493 1 0.034 1.379 1.025 1.857SSP Hu Overall 14.757 3 0.002SSP Hu (Luminal A vs basal-like) -0.12 0.514 0.054 1 0.816 0.887 0.324 2.43SSP Hu (Luminal B vs basal-like) 1.671 0.613 7.444 1 0.006 5.318 1.601 17.665SSP Hu (HER2 vs basal-like) 0.526 0.408 1.664 1 0.197 1.692 0.761 3.76

Lower UpperGRADE (1 vs 2 vs 3) 2.055 2 0.358GRADE 2 vs 1 0.134 0.428 0.098 1 0.754 1.144 0.494 2.648GRADE 3 vs 1 -0.369 0.499 0.549 1 0.459 0.691 0.26 1.837ER (Positive vs Negative) -0.627 0.356 3.112 1 0.078 0.534 0.266 1.072TUMOUR SIZE 0.342 0.154 4.927 1 0.026 1.408 1.041 1.903SSP Parker 3.68 4 0.451SSP Parker (Luminal A vs basal-like) -0.44 0.529 0.691 1 0.406 0.644 0.228 1.818SSP Parker (Luminal B vs basal-like) 0.211 0.418 0.256 1 0.613 1.235 0.545 2.802SSP Parker (Normal breast-like vs basal-like) 0.164 0.708 0.054 1 0.817 1.178 0.294 4.72SSP Parker (HER2 vs basal-like) 0.069 0.582 0.014 1 0.905 1.072 0.342 3.354

Lower UpperGRADE (1 vs 2 vs 3) 2.064 2 0.356GRADE 2 vs 1 0.174 0.428 0.166 1 0.684 1.19 0.515 2.754GRADE 3 vs 1 -0.359 0.516 0.484 1 0.486 0.698 0.254 1.919ER (Positive vs Negative) -0.524 0.338 2.399 1 0.121 0.592 0.305 1.149TUMOUR SIZE 0.388 0.147 6.977 1 0.008 1.474 1.105 1.966SSP Sorlie cut-off <0.1 Overall 5.071 4 0.28SSP Sorlie (Luminal A vs basal-like) -0.464 0.583 0.633 1 0.426 0.629 0.201 1.972SSP Sorlie (Luminal B vs basal-like) 0.112 0.421 0.071 1 0.789 1.119 0.491 2.552SSP Sorlie (HER2 vs basal-like) 1.068 0.622 2.947 1 0.086 2.909 0.86 9.844SSP Sorlie (Unclassifiable vs basal-like) 0.011 0.517 0 1 0.984 1.011 0.367 2.786

Lower UpperGRADE (1 vs 2 vs 3) 2.962 2 0.227GRADE 2 vs 1 0.26 0.43 0.364 1 0.546 1.297 0.558 3.014GRADE 3 vs 1 -0.373 0.494 0.57 1 0.45 0.689 0.262 1.813ER (Positive vs Negative) -0.788 0.384 4.222 1 0.04 0.455 0.214 0.964TUMOUR SIZE 0.333 0.153 4.715 1 0.03 1.394 1.033 1.883SSP Hu cut-off <0.1 Overall 16.122 4 0.003SSP Hu (Luminal A vs basal-like) -0.083 0.559 0.022 1 0.883 0.921 0.308 2.756SSP Hu (Luminal B vs basal-like) 1.697 0.637 7.1 1 0.008 5.46 1.567 19.032SSP Hu (HER2 vs basal-like) 0.099 0.554 .032 1 0.859 1.104 0.372 3.272SSP Hu (Unclassifiable vs basal-like) 0.623 0.457 1.859 1 0.173 1.865 .761 4.567

Lower UpperGRADE (1 vs 2 vs 3) 2.143 2 0.343GRADE 2 vs 1 0.153 0.43 0.126 1 0.722 1.165 0.502 2.704GRADE 3 vs 1 -0.366 0.499 0.536 1 0.464 0.694 0.261 1.846ER (Positive vs Negative) -0.635 0.359 3.131 1 0.077 0.53 0.262 1.071TUMOUR SIZE 0.339 0.154 4.855 1 0.028 1.404 1.038 1.898SSP Parker cut-off <0.1 Overall 3.898 5 0.564SSP Parker (Luminal A vs basal-like) -0.444 0.529 0.703 1 0.402 0.642 0.228 1.81SSP Parker (Luminal B vs basal-like) 0.217 0.42 0.268 1 0.605 1.243 0.546 2.83SSP Parker (Normal breast-like vs basal-like) 0.256 0.704 0.132 1 0.716 1.291 0.325 5.129SSP Parker (HER2 vs basal-like) 0.064 0.582 0.012 1 0.912 1.066 0.341 3.338SSP Parker (Unclassifiable vs basal-like) -0.208 1.089 0.037 1 0.848 0.812 0.096 6.867

TransBig dataset

Metastasis-free survival











P Value Hazard Ratio

95.0% CI for Hazard RatioB SE Wald


SSP Hu et al 2006




df


24

Lower UpperGRADE (1 vs 2 vs 3) 1.756 2 0.416GRADE 2 vs 1 -0.024 0.441 0.003 1 0.957 0.977 0.412 2.317GRADE 3 vs 1 -0.473 0.488 0.938 1 0.333 0.623 0.24 1.622ER (Positive vs Negative) -0.52 0.35 2.212 1 0.137 0.594 0.3 1.18TUMOUR SIZE 0.402 0.159 6.393 1 0.011 1.494 1.095 2.04SSP Sorlie Overall 7.185 4 0.126 0 0SSP Sorlie (Luminal A vs basal-like) -0.457 0.558 0.67 1 0.413 0.633 0.212 1.891SSP Sorlie (Luminal B vs basal-like) 0.258 0.439 0.345 1 0.557 1.294 0.547 3.062SSP Sorlie (Normal breast-like vs basal-like) -11.653 418.6 0.001 1 0.978 0 0 .SSP Sorlie (HER2 vs basal-like) 0.971 0.569 2.911 1 0.088 2.64 0.866 8.051

Lower UpperGRADE (1 vs 2 vs 3) 3.096 2 0.213GRADE 2 vs 1 0.075 0.44 0.029 1 0.864 1.078 0.455 2.555GRADE 3 vs 1 -0.618 0.512 1.457 1 0.227 0.539 0.197 1.471ER (Positive vs Negative) -0.789 0.406 3.779 1 0.052 0.454 0.205 1.007TUMOUR SIZE 0.299 0.158 3.587 1 0.058 1.349 0.99 1.838SSP Hu Overall 10.893 3 0.012SSP Hu (Luminal A vs basal-like) -0.25 0.54 0.214 1 0.644 0.779 0.27 2.244SSP Hu (Luminal B vs basal-like) 1.257 0.625 4.05 1 0.044 3.514 1.033 11.95SSP Hu (HER2 vs basal-like) 0.542 0.415 1.704 1 0.192 1.719 0.762 3.876

Lower UpperGRADE (1 vs 2 vs 3) 2.084 2 0.353GRADE 2 vs 1 -0.054 0.436 0.015 1 0.902 0.948 0.404 2.226GRADE 3 vs 1 -0.551 0.499 1.22 1 0.269 0.576 0.217 1.533ER (Positive vs Negative) -0.666 0.37 3.245 1 0.072 0.514 0.249 1.06TUMOUR SIZE 0.301 0.162 3.46 1 0.063 1.351 0.984 1.856SSP Parker Overall 5.499 4 0.24SSP Parker (Luminal A vs basal-like) -0.635 0.561 1.281 1 0.258 0.53 0.177 1.591SSP Parker (Luminal B vs basal-like) 0.189 0.425 0.198 1 0.657 1.208 0.525 2.781SSP Parker (Normal breast-like vs basal-like) -0.908 1.083 0.704 1 0.402 0.403 0.048 3.368SSP Parker (HER2 vs basal-like) 0.134 0.588 0.052 1 0.82 1.143 0.361 3.623

Lower UpperGRADE (1 vs 2 vs 3) 1.861 2 0.394GRADE 2 vs 1 -0.004 0.436 0 1 0.993 0.996 0.424 2.339GRADE 3 vs 1 -0.522 0.516 1.022 1 0.312 0.593 0.216 1.632ER (Positive vs Negative) -0.582 0.35 2.761 1 0.097 0.559 0.281 1.11TUMOUR SIZE 0.377 0.155 5.95 1 0.015 1.458 1.077 1.974SSP Sorlie cut-off <0.1 Overall 5.583 4 0.233SSP Sorlie (Luminal A vs basal-like) -0.447 0.622 0.516 1 0.472 0.64 0.189 2.164SSP Sorlie (Luminal B vs basal-like) 0.257 0.442 0.338 1 0.561 1.293 0.544 3.074SSP Sorlie (HER2 vs basal-like) 1.154 0.637 3.284 1 0.07 3.172 0.91 11.057SSP Sorlie (Unclassifiable vs basal-like) -0.05 0.56 0.008 1 0.929 0.951 0.317 2.852

Lower UpperGRADE (1 vs 2 vs 3) 2.21 2 0.331GRADE 2 vs 1 0.108 0.439 0.06 1 0.806 1.114 0.471 2.631GRADE 3 vs 1 -0.461 0.495 0.867 1 0.352 0.63 0.239 1.665ER (Positive vs Negative) -0.736 0.404 3.312 1 0.069 0.479 0.217 1.058TUMOUR SIZE 0.319 0.16 3.974 1 0.046 1.376 1.005 1.883SSP Hu cut-off <0.1 Overall 13.269 4 0.01SSP Hu (Luminal A vs basal-like) -0.218 0.591 0.136 1 0.712 0.804 0.252 2.563SSP Hu (Luminal B vs basal-like) 1.279 0.65 3.866 1 0.049 3.591 1.004 12.847SSP Hu (HER2 vs basal-like) 0.135 0.561 0.058 1 0.81 1.145 0.381 3.438SSP Hu (Unclassifiable vs basal-like) 0.708 0.47 2.265 1 0.132 2.03 0.807 5.102

Lower UpperGRADE (1 vs 2 vs 3) 2.123 2 0.346GRADE 2 vs 1 -0.047 0.438 0.011 1 0.915 0.954 0.405 2.249GRADE 3 vs 1 -0.555 0.499 1.235 1 0.266 0.574 0.216 1.528ER (Positive vs Negative) -0.682 0.373 3.333 1 0.068 0.506 0.243 1.051TUMOUR SIZE 0.303 0.162 3.516 1 0.061 1.354 0.986 1.859SSP Parker cut-off <0.1 Overall 5.326 5 0.377SSP Parker (Luminal A vs basal-like) -0.628 0.56 1.255 1 0.263 0.534 0.178 1.601SSP Parker (Luminal B vs basal-like) 0.198 0.427 0.216 1 0.642 1.22 0.528 2.818SSP Parker (Normal breast-like vs basal-like) -0.815 1.08 0.569 1 0.451 0.443 0.053 3.678SSP Parker (HER2 vs basal-like) 0.132 0.589 0.051 1 0.822 1.142 0.36 3.62SSP Parker (Unclassifiable vs basal-like) -0.114 1.093 0.011 1 0.917 0.892 0.105 7.607

NB: No information on histological grade and tumour size publicly available for Wang et al.9

Hazard Ratio








SSP Hu et al 2006


Overall survival

B SE Wald

Hazard Ratio


TransBig dataset




SSP Parker et al 2009, including unclassified cases, cut-off <0.1Hazard Ratio


SSP Sorlie et al 2003, including unclassified cases, cut-off <0.1Hazard Ratio


Hazard Ratio


25

P value* P value* P value* P value** P value** P value**Mean Standard Error of

MeanMean Standard Error

of MeanMean Standard Error of

MeanCount Row % Count Row % Count Row % Count Row % Count Row % Count Row % Count Row %

Basal-like 13 100.0 0 0.0 13 100.0 0 0.0 0 0.0 0 0.0 13 100.0 6.24124 0.23006 5.45480 0.02588 9.35966 0.12415Luminal A 1 14.3 6 85.7 7 100.0 0 0.0 0 0.0 0 0.0 7 100.0 11.67131 0.22305 5.51405 0.08396 8.59905 0.19879Luminal B 14 42.4 19 57.6 20 60.6 1 3.0 12 36.4 13 39.4 20 60.6 9.64934 0.40399 5.78949 0.08400 9.18079 0.11772

Basal-like 13 100.0 0 0.0 13 100.0 0 0.0 0 0.0 0 0.0 13 100.0 6.24124 0.23006 5.45480 0.02588 9.35966 0.12415Luminal A 1 16.7 5 83.3 6 100.0 0 0.0 0 0.0 0 0.0 6 100.0 11.84097 0.17131 5.52618 0.09830 8.67242 0.21860Luminal B 12 41.4 17 58.6 16 55.2 1 3.4 12 41.4 13 44.8 16 55.2 9.68533 0.44711 5.83653 0.09215 9.17753 0.10828Unclassifiable 2 40.0 3 60.0 5 100.0 0 0.0 0 0.0 0 0.0 5 100.0 9.64140 0.74134 5.44703 0.03707 8.99530 0.54713

Basal-like 14 100.0 0 0.0 13 92.9 0 0.0 1 7.1 1 7.1 13 92.9 6.31935 0.22687 5.54587 0.09417 9.40291 0.12281Luminal A 6 19.4 25 80.6 26 83.9 1 3.2 4 12.9 5 16.1 26 83.9 11.02550 0.23366 5.57181 0.05733 8.99152 0.13198HER2 8 100.0 0 0.0 1 12.5 0 0.0 7 87.5 7 87.5 1 12.5 6.37527 0.20953 6.27447 0.13282 9.30713 0.10447

Basal-like 12 100.0 0 0.0 12 100.0 0 0.0 0 0.0 0 0.0 12 100.0 6.13740 0.22318 5.45186 0.02795 9.38903 0.13114Luminal A 2 14.3 12 85.7 12 85.7 1 7.1 1 7.1 2 14.3 12 85.7 11.58130 0.21290 5.56119 0.06153 8.70604 0.16051Unclassifiable 14 51.9 13 48.1 16 59.3 0 0.0 11 40.7 11 40.7 16 59.3 9.09173 0.44471 5.82537 0.09925 9.26971 0.12309

Basal-like 13 100.0 0 0.0 13 100.0 0 0.0 0 0.0 0 0.0 13 100.0 6.24124 0.23006 5.45480 0.02588 9.35966 0.12415Luminal A 1 25.0 3 75.0 4 100.0 0 0.0 0 0.0 0 0.0 4 100.0 10.14677 0.70698 5.50181 0.04010 8.68479 0.32959Luminal B 14 38.9 22 61.1 23 63.9 1 2.8 12 33.3 13 36.1 23 63.9 9.98723 0.39032 5.76790 0.07924 9.12279 0.11358

Basal-like 13 100.0 0 0.0 13 100.0 0 0.0 0 0.0 0 0.0 13 100.0 6.24124 0.23006 5.45480 0.02588 9.35966 0.12415Luminal A 0 0.0 3 100.0 3 100.0 0 0.0 0 0.0 0 0.0 3 100.0 10.72479 0.57568 5.52576 0.04548 8.37413 0.15572Luminal B 13 37.1 22 62.9 22 62.9 1 2.9 12 34.3 13 37.1 22 62.9 9.98963 0.40163 5.77841 0.08082 9.12259 0.11687Unclassifiable 2 100.0 0 0.0 2 100.0 0 0.0 0 0.0 0 0.0 2 100.0 9.15793 0.74523 5.41496 0.01501 9.37311 0.24364

*: Chi-squared test; **: One-way ANOVA; SSP: Single sample predictor.NB: All tumours are grade III invasive ductal carcinomas of no special type.

SSP Hu et al 2006, cut-off <0.1


SSP Parker et al 2009, cut-off <0.1 0.0707

0.1705

0.1046<0.0001

<0.0001


SSP Sorlie et al 2003, cut-off <0.1

SSP Hu et al 2006

0.0451

0.0254

0.0130

<0.0001

0.0159

<0.0001

<0.0001

0.0332

0.1676

0.1018

0.0073

0.0001

0.0141

0.0171

0.0312

<0.001

0.0113

0.0868

0.1817

<0.0001

<0.0001

0.0004

0.0002

0.0054

0.0026

<0.0001

<0.0001

0.0002

0.0008

0.0336

0.0269

HER2 status FISH ESR1 ERBB2 AURKA

Supplementary Table 11: Correlations between molecular subtypes assigned by three single sample predictors (without and with correlation cut-off of <0.1) and oestrogen receptor (ER) as defined by immunohistochemistry, HER2 status as defined by immunohistochemistry and FISH, and average microarray-based gene expression levels of ESR1 , ERBB2 and AURKA in the 53 grade III invasive ductal carcinomas dataset.

ERNegative Positive

HER2 status ImmunohistochemistryNegative (0/1+) 3+2+ Amplified Not amplified

26

P value* P value** P value** P value** P value**Mean Standard Error of

MeanMean Standard Error of


MeanCount Row % Count Row % Count Row % Count Row % Count Row %

Basal-like 44 93.6 3 6.4 4 8.5 4 8.5 39 83.0 -3.85475 0.13634 -2.49622 0.15338 0.57282 0.09716Luminal A 0 0.0 96 100.0 41 42.7 42 43.8 13 13.5 0.54882 0.07570 -1.52174 0.07248 -0.52907 0.06950Luminal B 5 6.5 72 93.5 10 13.0 24 31.2 43 55.8 -0.41179 0.13360 -1.05271 0.17025 0.21125 0.09309Normal breast-like 2 6.9 27 93.1 14 48.3 11 37.9 4 13.8 -0.06075 0.19359 -1.31720 0.14330 -0.84617 0.09634HER2 18 39.1 28 60.9 6 13.0 20 43.5 20 43.5 -2.02309 0.22966 1.02060 0.26231 -0.18707 0.08409

Basal-like 44 95.7 2 4.3 3 6.5 4 8.7 39 84.8 -3.90162 0.13085 -2.49882 0.15672 0.60047 0.09519Luminal A 0 0.0 68 100.0 30 44.1 30 44.1 8 11.8 0.72947 0.08127 -1.49281 0.07748 -0.53929 0.08714Luminal B 5 10.0 45 90.0 5 10.0 11 22.0 34 68.0 -0.60722 0.18648 -0.79216 0.24060 0.37513 0.11422Normal breast-like 1 6.7 14 93.3 8 53.3 6 40.0 1 6.7 0.08288 0.28945 -1.09852 0.23348 -0.96834 0.11551HER2 17 43.6 22 56.4 3 7.7 17 43.6 19 48.7 -2.24249 0.24786 1.47649 0.24367 -0.12658 0.09061Unclassifiable 2 2.6 75 97.4 26 33.8 33 42.9 18 23.4 -0.11133 0.09590 -1.56830 0.08683 -0.40248 0.07689

Basal-like 48 85.7 8 14.3 3 5.4 9 16.1 44 78.6 -3.58493 0.16216 -2.02972 0.21833 0.57035 0.07102Luminal A 0 0.0 133 100.0 55 41.4 53 39.8 25 18.8 0.29437 0.07107 -1.44416 0.07526 -0.65191 0.05019Luminal B 0 0.0 48 100.0 9 18.8 20 41.7 19 39.6 0.24957 0.12656 -1.25531 0.19182 0.53396 0.09464Normal breast-like 4 19.0 17 81.0 7 33.3 10 47.6 4 19.0 -1.05740 0.29024 -1.29347 0.28559 -0.87554 0.13095HER2 17 45.9 20 54.1 1 2.7 9 24.3 27 73.0 -2.24831 0.24403 1.55233 0.20262 0.18308 0.09693

Basal-like 48 90.6 5 9.4 3 5.7 7 13.2 43 81.1 -3.72347 0.14984 -2.05612 0.23015 0.60331 0.07108Luminal A 0 0.0 127 100.0 54 42.5 51 40.2 22 17.3 0.33096 0.07139 -1.43945 0.07537 -0.67637 0.05014Luminal B 0 0.0 47 100.0 8 17.0 20 42.6 19 40.4 0.25856 0.12896 -1.25002 0.19587 0.55196 0.09491Normal breast-like 4 21.1 15 78.9 6 31.6 9 47.4 4 21.1 -1.01337 0.31984 -1.45735 0.24905 -0.91518 0.14034HER2 15 46.9 17 53.1 1 3.1 8 25.0 23 71.9 -2.36162 0.26038 1.87633 0.11162 0.18798 0.10735Unclassifiable 2 11.8 15 88.2 3 17.6 6 35.3 8 47.1 -1.00189 0.24775 -1.03158 0.38864 -0.08186 0.13263

Basal-like 45 93.8 3 6.3 5 10.4 4 8.3 39 81.3 -3.83219 0.14640 -2.50001 0.15432 0.56161 0.09773Luminal A 0 0.0 90 100.0 45 50.0 34 37.8 11 12.2 0.38935 0.08902 -1.35781 0.07993 -0.83509 0.04925Luminal B 0 0.0 78 100.0 12 15.4 35 44.9 31 39.7 0.27995 0.08866 -1.73580 0.10363 0.22820 0.07843Normal breast-like 2 8.0 23 92.0 9 36.0 10 40.0 6 24.0 -0.60102 0.20555 -1.05171 0.23424 -0.75841 0.12258HER2 22 40.7 32 59.3 4 7.4 18 33.3 32 59.3 -2.09121 0.19693 1.26240 0.19539 0.15954 0.08522

Basal-like 45 95.7 2 4.3 5 10.6 4 8.5 38 80.9 -3.90226 0.13131 -2.52214 0.15601 0.56847 0.09959Luminal A 0 0.0 89 100.0 45 50.6 33 37.1 11 12.4 0.39685 0.08970 -1.36357 0.08062 -0.83665 0.04978Luminal B 0 0.0 77 100.0 11 14.3 35 45.5 31 40.3 0.28812 0.08944 -1.74495 0.10457 0.23985 0.07857Normal breast-like 2 8.3 22 91.7 9 37.5 10 41.7 5 20.8 -0.56574 0.21112 -1.02855 0.24301 -0.75047 0.12753HER2 22 41.5 31 58.5 4 7.5 18 34.0 31 58.5 -2.11936 0.19862 1.31100 0.19285 0.17803 0.08477Unclassifiable 0 0.0 5 100.0 1 20.0 1 20.0 3 60.0 -0.64249 0.20977 -1.25146 0.13921 -0.57897 0.21053

*: Chi-squared test; **: One-way ANOVA; SSP: Single sample predictor.

ER

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

SSP Hu et al 2006



SSP Parker et al 2009, cut-off <0.1

<0.0001

<0.0001

<0.0001

<0.0001



<0.0001

<0.0001

Supplementary Table 12: Correlations between molecular subtypes assigned by three single sample predictors (without and with correlation cut-off of <0.1) and oestrogen receptor status (ER), histological grade, and average microarray-based gene expression levels of ESR1 , ERBB2 and AURKA in the ‘NKI-295’8 dataset.

3Histological grade ESR1

Negative Positive 1 2ERBB2 AURKA

27

P value* P value** P value** P value**Negative Positive Mean Standard Error of



MeanCount Row % Count Row %

Basal-like 39 79.59183673 10 20.40816327 4.337533752 0.045919033 5.256091134 0.061141965 6.657645997 0.058712444Luminal A 6 5.769230769 98 94.23076923 5.261400098 0.047004984 5.637477424 0.046745813 5.88733109 0.045006439Luminal B 23 18.5483871 101 81.4516129 4.864310448 0.036848257 5.995770578 0.078674228 6.401348463 0.048230512HER2 9 100 0 0 4.363861937 0.137055452 6.886448486 0.287713136 6.255970075 0.188208614

Basal-like 37 80.43478261 9 19.56521739 4.319996452 0.046726731 5.248971916 0.064442195 6.691157775 0.056409021Luminal A 5 5.882352941 80 94.11764706 5.318849999 0.054628826 5.635102427 0.05217393 5.911924581 0.048215245Luminal B 20 20 80 80 4.874363642 0.04239354 6.047466697 0.093787325 6.495978197 0.050514605HER2 7 100 0 0 4.446257915 0.155012848 6.878754127 0.262348438 6.440851458 0.148719995Unclassifiable 8 16.66666667 40 83.33333333 4.849828349 0.051033704 5.749277974 0.085540562 5.908070841 0.074543985

Basal-like 43 81.13207547 10 18.86792453 4.339353808 0.043477397 5.253442847 0.058593356 6.670395104 0.05803519Luminal A 9 5.263157895 162 94.73684211 5.145429725 0.036428286 5.73430554 0.044592714 5.969103886 0.036097373Luminal B 0 0 19 100 5.061575272 0.068198165 5.528998925 0.148615175 7.061524051 0.065253352Normal breast-like 1 100 0 0 4.448039828 . 5.56789583 . 6.033805388 .HER2 24 57.14285714 18 42.85714286 4.564328862 0.052522027 6.659097908 0.154949599 6.526846664 0.055174071

Basal-like 38 80.85106383 9 19.14893617 4.310771312 0.045430853 5.237763616 0.065028568 6.724083719 0.050744684Luminal A 6 3.947368421 146 96.05263158 5.180531067 0.037843726 5.725364809 0.044813097 5.944776107 0.037616562Luminal B 0 0 17 100 5.074929219 0.075771927 5.556525777 0.163866738 7.111449927 0.05738505HER2 16 76.19047619 5 23.80952381 4.441955853 0.045650897 7.325278544 0.125235096 6.57355752 0.071312443Unclassifiable 17 34.69387755 32 65.30612245 4.74637089 0.059713942 5.807705658 0.113851043 6.326546276 0.070216024

Basal-like 45 83.33333333 9 16.66666667 4.362073656 0.045522639 5.275272196 0.066625444 6.698511058 0.050170137Luminal A 3 4.615384615 62 95.38461538 5.068421025 0.055344583 5.731012229 0.068760789 5.757804641 0.054611276Luminal B 12 8.633093525 127 91.36690647 5.119621913 0.041024732 5.801804527 0.063271556 6.320032357 0.044372551Normal breast-like 5 38.46153846 8 61.53846154 4.596038424 0.102470903 5.868866607 0.181752152 5.792590463 0.1138991HER2 12 80 3 20 4.386581836 0.05323155 7.278207808 0.116490476 6.587530321 0.080923014

Basal-like 43 82.69230769 9 17.30769231 4.3437921 0.044506527 5.231201641 0.060615594 6.707210912 0.051620865Luminal A 3 4.918032787 58 95.08196721 5.095228712 0.057206291 5.72033663 0.065916155 5.723663173 0.051474309Luminal B 11 7.971014493 127 92.02898551 5.123515784 0.041136538 5.798968093 0.063667646 6.317651462 0.044630878Normal breast-like 4 36.36363636 7 63.63636364 4.644168567 0.115691131 5.732327 0.175124315 5.705046257 0.114966278HER2 12 80 3 20 4.386581836 0.05323155 7.278207808 0.116490476 6.587530321 0.080923014Unclassifiable 4 44.44444444 5 55.55555556 4.617568482 0.085776978 6.205597233 0.267663204 6.361693436 0.156178784





<0.0001<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

ER


SSP Hu et al 2006

SSP Sorlie et al 2003 <0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

AURKA

Supplementary Table 13: Correlations between molecular subtypes assigned by three single sample predictors (without and with correlation cut-off of <0.1) and oestrogen receptor status (ER) and average microarray-based gene expression levels of ESR1 , ERBB2 and AURKA in the ‘Wang’9 dataset.

<0.0001

NB: Data on histological grade not publicly available.

ESR1 ERBB2

<0.0001 <0.0001

<0.0001

<0.0001

28

P value* P value* P value** P value** P value**Mean Standard Error of



MeanCount Row % Count Row % Count Row % Count Row % Count Row %

Basal-like 24 80.0 6 20.0 0 0.0 6 20.7 23 79.3 3.82380 0.05674 5.37811 0.11773 6.55969 0.09519Luminal A 5 7.8 59 92.2 15 23.4 41 64.1 8 12.5 5.48328 0.08315 5.89791 0.08367 5.61616 0.06560Luminal B 25 27.8 65 72.2 13 14.6 33 37.1 43 48.3 4.80654 0.08978 6.02552 0.11795 6.23855 0.06141Normal breast-like 0 0.0 3 100.0 2 66.7 0 0.0 1 33.3 4.48239 0.38753 5.47970 0.47632 5.18378 0.06802HER2 10 90.9 1 9.1 0 0.0 3 27.3 8 72.7 3.75149 0.14359 7.14710 0.38754 6.35789 0.15374

Basal-like 24 80.0 6 20.0 0 0.0 6 20.7 23 79.3 3.82380 0.05674 5.37811 0.11773 6.55969 0.09519Luminal A 1 2.3 42 97.7 11 25.6 28 65.1 4 9.3 5.62145 0.10166 5.83728 0.10291 5.69083 0.08722Luminal B 23 35.4 42 64.6 6 9.2 17 26.2 42 64.6 4.73144 0.11653 6.11703 0.15370 6.41999 0.06346HER2 7 100.0 0 0.0 0 0.0 1 14.3 6 85.7 3.64147 0.12575 7.66257 0.35819 6.56290 0.12993Unclassifiable 9 17.0 44 83.0 13 25.0 31 59.6 8 15.4 4.97124 0.08893 5.89760 0.10229 5.63106 0.06581

Basal-like 32 80.0 8 20.0 0 0.0 7 17.9 32 82.1 3.79021 0.05405 5.24338 0.10777 6.57951 0.07380Luminal A 10 8.4 109 91.6 26 22.0 71 60.2 21 17.8 5.31543 0.06246 5.89879 0.06952 5.73343 0.04813Luminal B 0 0.0 9 100.0 2 22.2 2 22.2 5 55.6 5.50309 0.19698 6.01920 0.13992 6.73946 0.20528HER2 22 73.3 8 26.7 2 6.7 3 10.0 25 83.3 3.97577 0.10668 7.00999 0.25167 6.56898 0.07461

Basal-like 26 83.9 5 16.1 0 0.0 3 10.0 27 90.0 3.86459 0.05525 5.36111 0.11340 6.65467 0.06844Luminal A 7 6.4 103 93.6 25 22.9 67 61.5 17 15.6 5.32739 0.06284 5.87697 0.06937 5.68442 0.04845Luminal B 0 0.0 9 100.0 2 22.2 2 22.2 5 55.6 5.50309 0.19698 6.01920 0.13992 6.73946 0.20528HER2 13 86.7 2 13.3 0 0.0 1 6.7 14 93.3 3.93842 0.18556 7.71524 0.23966 6.67455 0.12313Unclassifiable 18 54.5 15 45.5 3 9.1 10 30.3 20 60.6 4.19776 0.15007 5.86668 0.22831 6.38875 0.07370

Basal-like 34 82.9 7 17.1 1 2.5 6 15.0 33 82.5 3.84860 0.05428 5.34587 0.11445 6.54971 0.07345Luminal A 3 4.8 60 95.2 17 27.0 41 65.1 5 7.9 5.27830 0.07722 5.92998 0.07022 5.51148 0.06176Luminal B 14 18.7 61 81.3 10 13.5 29 39.2 35 47.3 5.14066 0.10609 5.98569 0.12129 6.27971 0.06112Normal breast-like 2 25.0 6 75.0 2 25.0 5 62.5 1 12.5 4.62974 0.16756 5.68580 0.29747 5.54924 0.14576HER2 11 100.0 0 0.0 0 0.0 2 18.2 9 81.8 3.63929 0.12883 8.08921 0.17048 6.54987 0.11713

Basal-like 34 82.9 7 17.1 1 2.5 6 15.0 33 82.5 3.84860 0.05428 5.34587 0.11445 6.54971 0.07345Luminal A 3 4.8 60 95.2 17 27.0 41 65.1 5 7.9 5.27830 0.07722 5.92998 0.07022 5.51148 0.06176Luminal B 13 17.8 60 82.2 10 13.9 27 37.5 35 48.6 5.17399 0.10630 5.96981 0.12366 6.28707 0.06220Normal breast-like 2 28.6 5 71.4 2 28.6 4 57.1 1 14.3 4.57251 0.18185 5.68754 0.34348 5.49945 0.15819HER2 11 100.0 0 0.0 0 0.0 2 18.2 9 81.8 3.63929 0.12883 8.08921 0.17048 6.54987 0.11713Unclassifiable 1 33.3 2 66.7 0 0.0 3 100.0 0 0.0 4.29286 0.37656 6.26823 0.43099 5.97350 0.20955

Supplementary Table 14: Correlations between molecular subtypes assigned by three single sample predictors (without and with correlation cut-off of <0.1) and oestrogen receptor status (ER), histological grade, and average microarray-based gene expression levels of ESR1 , ERBB2 and AURKA in the ‘TransBig’10 dataset.

AURKANegative Positive 1 2 3

GRADE ESR1 ERBB2



SSP Hu et al 2006


<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001



<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001


ER

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

29

SSP/ Centroid ProbesProbes with

updated annotation

53 Grade III IDC dataset

NKI 295 dataset Wang dataset TransBig dataset

Sorlie 2003 498 424 488 280 578 579Hu 2006 305 305 380 241 504 507

Parker 2009 50 50 66 45 78 79


updated annotation



Sorlie 2003 498 425 376 243 357 356Hu 2006 305 305 281 218 281 281

Parker 2009 50 50 48 36 41 41


updated annotation



Sorlie 2003 498 418 525 306 577 577Hu 2006 305 297 393 234 490 490

Parker 2009 50 50 66 40 77 77


updated annotation



Sorlie 2003 498 419 398 306 367 367Hu 2006 305 298 289 234 279 279

Parker 2009 50 50 49 40 43 43


updated annotation



Sorlie 2003 498 453 342 503 560 562Hu 2006 305 284 205 320 441 441

Parker 2009 50 50 44 55 78 79


updated annotation



Sorlie 2003 498 454 283 395 346 346Hu 2006 305 284 160 256 250 250

Parker 2009 50 50 35 47 40 40

Supplementary Table 15: Probes/ unique genes identified for each centroid/SSP gene list and breast cancer dataset using HUGO gene symbols, Ensembl gene identifiers and Unigene cluster identifiers. SSP: single sample predictor.

Unigene cluster identifier overlays, all probes

Unigene cluster identifier overlays, unique genes

HUGO gene symbol overlays, all probes

HUGO gene symbol overlays, unique genes

Ensembl gene identifier overlays, all probes

Ensembl gene identifier overlays, unique genes

30

Supplementary figure 1: (A) Molecular subtype classification of the ‘NKI-295’8 breast cancers using three distinct single sample predictors, oestrogen receptor (ER) status, histological grade, lymph node status and tumour size, and Kaplan-Meier curves (P value from log-rank test) of breast cancer patients assigned to the molecular subtype classes using the single sample predictors (SSPs) by (B) Sorlie et al4, (C) Hu et al5 and (D) Parker et al6 for metastasis-free survival.

Data on ER status, histological grade, lymph node status and tumour size retrieved from http://microarray-pubs.stanford.edu/wound_NKI/explore.html.

31

Supplementary figure 2: (A) Molecular subtype classification of the ‘NKI-295’8 breast cancers including unclassified cases (cut-off <0.1) using three distinct single sample predictors, ER status, histological grade, lymph node status and tumour size, and Kaplan-Meier curves (P value from log-rank test) of breast cancer patients assigned to the molecular subtype classes using the single sample predictors by (B) Sorlie et al4, (C) Hu et al5 and (D) Parker et al6 for overall survival.


32

Supplementary figure 3: (A) Molecular subtype classification of the ‘NKI-295’8 breast cancers including unclassified cases (cut-off <0.1) using three distinct single sample predictors, oestrogen receptor (ER) status, histological grade, lymph node status and tumour size, and Kaplan-Meier curves (P value from log-rank test) of breast cancer patients assigned to the molecular subtype classes using the single sample predictors (SSPs) by (B) Sorlie et al4, (C) Hu et al5 and (D) Parker et al6 for metastasis-free survival.


33

Supplementary figure 4: (A) Molecular subtype classification of 286 ‘Wang’9 breast tumours including unclassified cases (cut-off <0.1) using three distinct single sample predictors and oestrogen receptor (ER) status, and Kaplan-Meier curves (P value from log-rank test) of breast cancer patients assigned to the molecular subtype classes using the single sample predictors (SSPs) by (B) Sorlie et al4, (C) Hu et al5 and (D) Parker et al6 for metastasis-free survival.

Data on ER status retrieved from GEO:GSE2034.

34

Supplementary figure 5: (A) Molecular subtype classification of 198 ‘TransBig’10 breast cancers using three distinct single sample predictors, oestrogen receptor (ER) status, histological grade, tumour size, and Kaplan-Meier curves (P value from log-rank test) of breast cancer patients assigned to the molecular subtype classes using the single sample predictors (SSPs) by (B) Sorlie et al4, (C) Hu et al5 and (D) Parker et al6 for metastasis-free survival.

Data on ER status, histological grade and tumour size retrieved from GEO:GSE7390.

35

Supplementary figure 6: (A) Molecular subtype classification of 198 ‘TransBig’10 breast cancers including unclassified cases (cut-off <0.1) using three distinct single sample predictors, oestrogen receptor (ER) status, histological grade, tumour size, and Kaplan-Meier curves (P value from log-rank test) of breast cancer patients assigned to the molecular subtype classes using the single sample predictors (SSPs) by (B) Sorlie et al4, (C) Hu et al5 and (D) Parker et al6 for overall survival.


36

Supplementary figure 7: (A) Molecular subtype classification of 198 ‘TransBig’10 breast cancers including unclassified cases (cut-off <0.1) using three distinct single sample predictors, oestrogen receptor (ER) status, histological grade, tumour size, and Kaplan-Meier curves (P value from log-rank test) of breast cancer patients assigned to the molecular subtype classes using the single sample predictors (SSPs) by (B) Sorlie et al4, (C) Hu et al5 and (D) Parker et al6 for metastasis-free survival.


37

Supplementary figure 8: Microarray-based mRNA expression levels of (A) ESR1, (B) PGR, (C) ERBB2, (D) GRB7, (E) AURKA and (F) MKI67 in 53 grade III invasive ductal carcinomas according to molecular subtypes assigned using the single sample predictor (SSP) by Sorlie et al4. Error bars represent standard deviation of mean.

38

Supplementary figure 9: Microarray-based mRNA expression levels of (A) ESR1, (B) PGR, (C) ERBB2, (D) GRB7, (E) AURKA and (F) MKI67 in 53 grade III invasive ductal carcinomas according to molecular subtypes including unclassified cases (cut-off <0.1) assigned using the single sample predictor (SSP) by Sorlie et al4. Error bars represent standard deviation of mean.

39

Supplementary figure 10: Microarray-based mRNA expression levels of (A) ESR1, (B) PGR, (C) ERBB2, (D) GRB7, (E) AURKA and (F) MKI67 in 53 grade III invasive ductal carcinomas according to molecular subtypes assigned using the single sample predictor (SSP) by Hu et al5. Error bars represent standard deviation of mean.

40

Supplementary figure 11: Microarray-based mRNA expression levels of (A) ESR1, (B) PGR, (C) ERBB2, (D) GRB7, (E) AURKA and (F) MKI67 in 53 grade III invasive ductal carcinomas according to molecular subtypes including unclassified cases (cut-off <0.1) assigned using the single sample predictor (SSP) by Hu et al5. Error bars represent standard deviation of mean.

41

Supplementary figure 12: Microarray-based mRNA expression levels of (A) ESR1, (B) PGR, (C) ERBB2, (D) GRB7, (E) AURKA and (F) MKI67 in 53 grade III invasive ductal carcinomas according to molecular subtypes assigned using the single sample predictor (SSP) by Parker et al6. Error bars represent standard deviation of mean.

42

Supplementary figure 13: Microarray-based mRNA expression levels of (A) ESR1, (B) PGR, (C) ERBB2, (D) GRB7, (E) AURKA and (F) MKI67 in 53 grade III invasive ductal carcinomas according to molecular subtypes including unclassified cases (cut-off <0.1) assigned using the single sample predictor (SSP) by Parker et al6. Error bars represent standard deviation of mean.

43

Supplementary figure 14: Microarray-based mRNA expression levels of (A) ESR1, (B) PGR, (C) ERBB2, (D) GRB7, (E) AURKA and (F) MKI67 in the ‘NKI-295’8 dataset cancers according to molecular subtypes assigned using the single sample predictor (SSP) by Sorlie et al4. Error bars represent standard deviation of mean.

44

Supplementary figure 15: Microarray-based mRNA expression levels of (A) ESR1, (B) PGR, (C) ERBB2, (D) GRB7, (E) AURKA and (F) MKI67 in the ‘NKI-295’8 dataset cancers according to molecular subtypes including unclassified cases (cut-off <0.1) assigned using the single sample predictor (SSP) by Sorlie et al4. Error bars represent standard deviation of mean.

45

Supplementary figure 16: Microarray-based mRNA expression levels of (A) ESR1, (B) PGR, (C) ERBB2, (D) GRB7, (E) AURKA and (F) MKI67 in the ‘NKI-295’8 dataset cancers according to molecular subtypes assigned using the single sample predictor (SSP) by Hu et al5. Error bars represent standard deviation of mean.

46

Supplementary figure 17: Microarray-based mRNA expression levels of (A) ESR1, (B) PGR, (C) ERBB2, (D) GRB7, (E) AURKA and (F) MKI67 in the ‘NKI-295’8 dataset cancers according to molecular subtypes including unclassified cases (cut-off <0.1) assigned using the single sample predictor (SSP) by Hu et al5. Error bars represent standard deviation of mean.

47

Supplementary figure 18: Microarray-based mRNA expression levels of (A) ESR1, (B) PGR, (C) ERBB2, (D) GRB7, (E) AURKA and (F) MKI67 in the ‘NKI-295’8 dataset cancers according to molecular subtypes assigned using the single sample predictor (SSP) by Parker et al6. Error bars represent standard deviation of mean.

48

Supplementary figure 19: Microarray-based mRNA expression levels of (A) ESR1, (B) PGR, (C) ERBB2, (D) GRB7, (E) AURKA and (F) MKI67 in the ‘NKI-295’8 dataset cancers according to molecular subtypes including unclassified cases (cut-off <0.1) assigned using the single sample predictor (SSP) by Parker et al6. Error bars represent standard deviation of mean.

49

Supplementary figure 20: Microarray-based mRNA expression levels of (A) ESR1, (B) PGR, (C) ERBB2, (D) GRB7, (E) AURKA and (F) MKI67 in the ‘Wang’9 dataset cancers according to molecular subtypes assigned using the single sample predictor (SSP) by Sorlie et al4. Error bars represent standard deviation of mean.

50

Supplementary figure 21: Microarray-based mRNA expression levels of (A) ESR1, (B) PGR, (C) ERBB2, (D) GRB7, (E) AURKA and (F) MKI67 in the ‘Wang’9 dataset cancers according to molecular subtypes including unclassified cases (cut-off <0.1) assigned using the single sample predictor (SSP) by Sorlie et al4. Error bars represent standard deviation of mean.

51

Supplementary figure 22: Microarray-based mRNA expression levels of (A) ESR1, (B) PGR, (C) ERBB2, (D) GRB7, (E) AURKA and (F) MKI67 in the ‘Wang’9 dataset cancers according to molecular subtypes assigned using the single sample predictor (SSP) by Hu et al5. Error bars represent standard deviation of mean.

52

Supplementary figure 23: Microarray-based mRNA expression levels of (A) ESR1, (B) PGR, (C) ERBB2, (D) GRB7, (E) AURKA and (F) MKI67 in the ‘Wang’9 dataset cancers according to molecular subtypes including unclassified cases (cut-off <0.1) assigned using the single sample predictor (SSP) by Hu et al5. Error bars represent standard deviation of mean.

53

Supplementary figure 24: Microarray-based mRNA expression levels of (A) ESR1, (B) PGR, (C) ERBB2, (D) GRB7, (E) AURKA and (F) MKI67 in the ‘Wang’9 dataset cancers according to molecular subtypes assigned using the single sample predictor (SSP) by Parker et al6. Error bars represent standard deviation of mean.

54

Supplementary figure 25: Microarray-based mRNA expression levels of (A) ESR1, (B) PGR, (C) ERBB2, (D) GRB7, (E) AURKA and (F) MKI67 in the ‘Wang’9 dataset cancers according to molecular subtypes including unclassified cases (cut-off <0.1) assigned using the single sample predictor (SSP) by Parker et al6. Error bars represent standard deviation of mean.

55

Supplementary figure 26: Microarray-based mRNA expression levels of (A) ESR1, (B) PGR, (C) ERBB2, (D) GRB7, (E) AURKA and (F) MKI67 in the ‘TransBig’10 dataset cancers according to molecular subtypes assigned using the single sample predictor (SSP) by Sorlie et al4. Error bars represent standard deviation of mean.

56

Supplementary figure 27: Microarray-based mRNA expression levels of (A) ESR1, (B) PGR, (C) ERBB2, (D) GRB7, (E) AURKA and (F) MKI67 in the ‘TransBig’10 dataset cancers according to molecular subtypes including unclassified cases (cut-off <0.1) assigned using the single sample predictor (SSP) by Sorlie et al4. Error bars represent standard deviation of mean.

57

Supplementary figure 28: Microarray-based mRNA expression levels of (A) ESR1, (B) PGR, (C) ERBB2, (D) GRB7, (E) AURKA and (F) MKI67 in the ‘TransBig’10 dataset cancers according to molecular subtypes assigned using the single sample predictor (SSP) by Hu et al5. Error bars represent standard deviation of mean.

58

Supplementary figure 29: Microarray-based mRNA expression levels of (A) ESR1, (B) PGR, (C) ERBB2, (D) GRB7, (E) AURKA and (F) MKI67 in the ‘TransBig’10 dataset cancers according to molecular subtypes including unclassified cases (cut-off <0.1) assigned using the single sample predictor (SSP) by Hu et al5. Error bars represent standard deviation of mean.

59

Supplementary figure 30: Microarray-based mRNA expression levels of (A) ESR1, (B) PGR, (C) ERBB2, (D) GRB7, (E) AURKA and (F) MKI67 in the ‘TransBig’10 dataset cancers according to molecular subtypes assigned using the single sample predictor (SSP) by Parker et al6. Error bars represent standard deviation of mean.

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Supplementary figure 31: Microarray-based mRNA expression levels of (A) ESR1, (B) PGR, (C) ERBB2, (D) GRB7, (E) AURKA and (F) MKI67 in the ‘TransBig’10 dataset cancers according to molecular subtypes including unclassified cases (cut-off <0.1) assigned using the single sample predictor (SSP) by Parker et al6. Error bars represent standard deviation of mean.

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ExpressionSet Nearest Centroid Correlations

Alan Mackay

January 5, 2010

This document describes the R code used to perform centroid correlationsusing ExpressionSet objects in R. It is written to accompany ”Breast cancermolecular profiling: a retrospective analysis of molecular subtype assignmentusing single sample predictors” by Britta Weigelt, Alan Mackay, Roger A’Hern,Rachael Natrajan, David Tan, Mitch Dowsett, Alan Ashworth, and Jorge SReis-Filho. This document was written using Sweave and LaTeX such that allthe R code contained herein is evaluable and can be used to recreate the centroidcorrelation results described in Weigelt et al. This represents an aspiration tofulfill the requirements of reproducible research http://reproducibleresearch.net.The R code uses ExpressionSets to hold genomic data as the core S4 class of theBiobase package and the standard for data analysis in R using Bioconductor.

1 Centroids used for correlations

The annotation of centroid gene lists and breast cancer datasets used here wascomprehensively updated and mapped to build 36 of the human genome (En-sembl assembly 54). HUGO gene symbols, Ensembl gene identifiers (IDs) andupdated Unigene cluster IDs were used to annotate each centroid gene list.

The genes of the centroids/ single sample predictors (SSPs) published by Sor-lie et al (1), Hu et al (2) and Parker et al (3) were retrieved from the Stanford Mi-croarray Database (http:// smd.stanford.edu/) or University of North CarolinaMicroarray Database (https://genome.unc.edu/cgi-bin/SMD/umad.pl). IMAGEclone IDs of the 500 gene centroids published by Sorlie et al (1) were updated andannotated using SOURCE (http://smd.stanford.edu/cgi-bin/source/sourceSearch)and merged with Ensembl gene IDs using entrez gene numbers. HUGO genesymbols, Unigene and Ensembl IDs for the 306 gene centroids by Hu et al (2)were retrieved directly from Biomart (www.ensembl.org/biomart/index.html)using the Agilent probe IDs supplied by the authors. The 50 gene centroids(PAM50) described by Parker et al (3) were annotated using SOURCE as de-scribed above based upon the HUGO gene symbols described in the supplemen-tary information supplied by the authors.

Published centroids with updated annotation can be loaded with the code

> Hu.centroids <- read.delim("http://rock.icr.ac.uk/

collaborations/Mackay/centroid.correlations.Eset/Hu306.centroids.txt",

+ header = T, sep = "\t", stringsAsFactors = F)

> names(Hu.centroids)

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[1] "LuminalB" "LuminalA" "Normal" "Basal"

[5] "HER2" "Agilent.ID" "symbol" "description"

[9] "Aliases" "accession" "unigene" "ensg"

[13] "entrez"

> Sorlie.centroids <- read.delim("http://rock.icr.ac.uk/

collaborations/Mackay/centroid.correlations.Eset/Sorlie500.centroids.txt",


> names(Sorlie.centroids)

[1] "Normal" "HER2" "LuminalA" "LuminalB"

[5] "Basal" "cloneID" "symbol" "description"

[9] "alias" "accession" "unigene" "ensg"

[13] "entrez"

> PAM50.centroids <- read.delim("http://rock.icr.ac.uk/

collaborations/Mackay/centroid.correlations.Eset/PAM50.centroids.txt",


> names(PAM50.centroids)

[1] "Basal" "HER2" "LuminalA" "LuminalB"

[5] "Normal" "symbol" "description" "alias"

[9] "accession" "unigene" "ensg" "entrez"

2 ExpressionSet objects for datasets used

2.1 NKI295 dataset

Gene expression data for the 295 breast cancers published by van de Vijver et al(4) is available at http://microarray-pubs.stanford.edu/wound NKI/explore.html.Pre-processed and normalised gene expression data provided by the authors isused here for centroid correlations.

Gene expression data and phenoData can be read into an ExpressionSet ”NKI295”with the code

> NKI295 <- readExpressionSet(exprsFile = "http://rock.icr.ac.uk/

collaborations/Mackay/centroid.correlations.Eset/NKI295.exprs.txt",

+ sep = "\t", header = T, stringsAsFactors = F,

+ na.strings = c("", "NA", "N/A"))

> pData(NKI295) <- read.table("http://rock.icr.ac.uk/

collaborations/Mackay/centroid.correlations.Eset/NKI295.pdata.txt",



FeatureData annotation of the NKI295 dataset used here was based upon acces-sion numbers and the Phil Green Contig identifiers provided. Genbank acces-sions were annotated using SOURCE and merged with Ensembl gene IDs using

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63

entrez gene numbers as described above for centroid annoatation. Ensembl an-notation from NCBI build 36 assembly 54 was merged with this annotationbased upon Entrez Gene identifiers.

FeatureData annotation of the NKI295 dataset can be read with the code

> NKI295.fdata <- read.table("http://rock.icr.ac.uk/

collaborations/Mackay/centroid.correlations.Eset/NKI295.fdata.txt",



All probeIDs in the featureData file match those in the NKI295 ExpressionSet

> all(featureNames(NKI295) == NKI295.fdata$probeID)

[1] TRUE

featureData of NKI295 ExpressionSet is annotated with the code

> fData(NKI295)$probeID <- NKI295.fdata$probeID

> fData(NKI295)$symbol <- NKI295.fdata$symbol

> fData(NKI295)$description <- NKI295.fdata$description

> fData(NKI295)$accession <- NKI295.fdata$accession

> fData(NKI295)$ensg <- NKI295.fdata$ensg

> fData(NKI295)$unigene <- NKI295.fdata$unigene

MetaData is added to describe the feature Data annotation in the NKI295dataset with the code

> fvarMetadata(NKI295)$labelDescription <- c("probe identifier",

+ "gene symbol", "gene description", "accession number",

+ "ensembl gene ID", "unigene cluster ID")

> fvarMetadata(NKI295)

labelDescription

probeID probe identifier

symbol gene symbol

description gene description

accession accession number

ensg ensembl gene ID

unigene unigene cluster ID

MetaData was added to describe the phenoData in the NKI295 ExpressionSetwith the code chunk below. phenoData includes the previously published nearestcentroid correlations for this dataset.

> varMetadata(NKI295)$labelDescription <- c("Training or validation",

+ "Even death", "Distant metastsis", "Surivial - death",

+ "time to recurrence", "Tumour size", "Size over 2cm",

+ "Nodal status", "Tumour grade", "Estrogen receptor status",

+ "Age", "70 gene signature", "Sorlie correlation",

+ "Sorlie correlation > 0.1", "Sorlie Normal correlation",

+ "Sorlie ERBB2 correlation", "Sorlie Luminal A correlation",

+ "Sorlie Luminal B correlation", "Sorlie Basal correlation",

+ "Nearest centroid (Fan)")

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64

> varMetadata(NKI295)

labelDescription

Label_Traing_and_Validation Training or validation

event_death Even death

Distant_metastasis_as_first_event.MCR. Distant metastsis

survival.death. Surivial - death

timerecu.MCR. time to recurrence

diameter.mm. Tumour size

size Size over 2cm

node Nodal status

grade Tumour grade

ER Estrogen receptor status

Age.years. Age

X70_genes 70 gene signature

Sorlie_Corr_5 Sorlie correlation

Sorlie_cor_CutOff_0.1 Sorlie correlation > 0.1

Cor.Normal Sorlie Normal correlation

Cor.ERBB2 Sorlie ERBB2 correlation

Cor.LumA Sorlie Luminal A correlation

Cor.LumB Sorlie Luminal B correlation

Cor.Basal Sorlie Basal correlation

Fan.nearest.centroid Nearest centroid (Fan)

This completes the NKI295 ExpressionSet

> validObject(NKI295)

[1] TRUE

> NKI295

ExpressionSet (storageMode: lockedEnvironment)

assayData: 24481 features, 295 samples

element names: exprs

phenoData

sampleNames: NKI295_4, NKI295_6, ..., NKI295_404 (295 total)

varLabels and varMetadata description:

Label_Traing_and_Validation: Training or validation

event_death: Even death

...: ...

Fan.nearest.centroid: Nearest centroid (Fan)

(20 total)

featureData

featureNames: 16, 17, ..., 24496 (24481 total)

fvarLabels and fvarMetadata description:

probeID: probe identifier

symbol: gene symbol

...: ...

unigene: unigene cluster ID

(6 total)

experimentData: use 'experimentData(object)'Annotation:

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65

2.2 Wang dataset

Gene expression data for 286 node negative breast cancers published by Wang etal (5) was retrieved from Gene Expression Omnibus (GEO) with the accessionGSE2034 http://www.ncbi.nlm.nih.gov/projects/geo/. Raw CEL files from theAffymetrix U133A array were read and normalised using mas5 in the affy pack-age.

Gene expression data and phenoData can be loaded into an ExpressionSet”wang” with the code

> wang <- readExpressionSet(exprsFile = "http://rock.icr.ac.uk/

collaborations/Mackay/centroid.correlations.Eset/wang.exprs.txt",

+ phenoDataFile = "http://rock.icr.ac.uk/

collaborations/Mackay/centroid.correlations.Eset/wang.pdata.txt",


+ na.strings = c("", "NA", "N/A"), row.names = 1, quote = "\"")

FeatureData annotation of the Wang dataset was based upon the AffymetrixprobeID. probeIDs for the U133A array were used to retrieve annotation fromensembl 54 using Biomart.

FeatureData annotation of the Wang dataset can be read with the code

> wang.fdata <- read.table("http://rock.icr.ac.uk/

collaborations/Mackay/centroid.correlations.Eset/wang.fdata.txt",



All probeIDs in the featureData file match those in the Wang ExpressionSet

> all(featureNames(wang) == wang.fdata$probeID)

[1] TRUE

FeatureData of Wang ExpressionSet is annotated with the code

> fData(wang)$probeID <- wang.fdata$probeID

> fData(wang)$symbol <- wang.fdata$symbol

> fData(wang)$description <- wang.fdata$description

> fData(wang)$accession <- wang.fdata$accession

> fData(wang)$ensg <- wang.fdata$ensg

> fData(wang)$unigene <- wang.fdata$unigene

MetaData is added to describe the feature Data annotation in the Wang Ex-pressionSet with the code

> fvarMetadata(wang)$labelDescription <- c(

+ "Affymetrix probe identifier", "gene symbol",

+ "gene description", "accession number",


> fvarMetadata(wang)

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66

labelDescription

probeID Affymetrix probe identifier

symbol gene symbol





MetaData was added to describe the phenoData in the Wang ExpressionSetwith the code

> varMetadata(wang)$labelDescription <- c(

+ "time of distant metastasis free survival",

+ "metastasis events", "Estrogen receptor status",

+ "tumour size", "patient age", "tumour grade")

> varMetadata(wang)

labelDescription

t.dmfs..years. time of distant metastasis free survival

e.dmfs metastasis events


tumor.size..cm. tumour size

age patient age

grade tumour grade

This completes the Wang ExpressionSet

> validObject(wang)

[1] TRUE

> wang




phenoData

sampleNames: GSM36777, GSM36778, ..., GSM37062 (286 total)


t.dmfs..years.: time of distant metastasis free survival

e.dmfs: metastasis events

...: ...

grade: tumour grade

(6 total)

featureData

featureNames: 1007_s_at, 1053_at, ...,

AFFX-r2-P1-cre-5_at (22283 total)


probeID: Affymetrix probe identifier

symbol: gene symbol

...: ...

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67


(6 total)


2.3 Transbig dataset

Gene expression data for 198 node negative breast cancers published by Desmedtet al (6) and referred to as the Transbig dataset was retrieved from Gene Ex-pression Omnibus (GEO; http://www.ncbi.nlm.nih.gov/geo/) with the acces-sion number GSE7390. Raw CEL files from the Affymetrix U133A array wereread and normalised using mas5 in the affy package.

Gene expression data and phenoData can be loaded into an ExpressionSet”transbig” with the code

> transbig <- readExpressionSet(exprsFile = "http://rock.icr.ac.uk/

collaborations/Mackay/centroid.correlations.Eset/transbig.exprs.txt",


collaborations/Mackay/centroid.correlations.Eset/transbig.pdata.txt",

+ sep = "\t", header = T, stringsAsFactors = F, na.strings = c("",

+ na.strings = c("", "NA", "N/A"), row.names = 1)

FeatureData annotation of the Transbig dataset was also based upon the AffymetrixprobeID. probeIDs for the U133A array were used to retrieve annotation fromensembl 54 using Biomart.

FeatureData annotation of the Transbig dataset can be read with the code

> transbig.fdata <- read.table("http://rock.icr.ac.uk/

collaborations/Mackay/centroid.correlations.Eset/transbig.fdata.txt",



All probeIDs in the featureData file match those in the Transbig ExpressionSet

> all(featureNames(transbig) == transbig.fdata$probeID)

[1] TRUE

FeatureData of the Transbig ExpressionSet is annotated with the code

> fData(transbig)$probeID <- transbig.fdata$probeID

> fData(transbig)$symbol <- transbig.fdata$symbol

> fData(transbig)$description <- transbig.fdata$description

> fData(transbig)$accession <- transbig.fdata$accession

> fData(transbig)$ensg <- transbig.fdata$ensg

> fData(transbig)$unigene <- transbig.fdata$unigene

MetaData is added to describe the feature Data annotation in the TransbigExpressionSet with the code

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68

> fvarMetadata(transbig)$labelDescription <- c(

+ "Affymetrix probe identifier", "gene symbol",

+ "gene description", "accession number",


> fvarMetadata(transbig)

labelDescription

probeID Affymetrix probe identifier

symbol gene symbol





MetaData is added to describe the phenoData in the Transbig dataset with thecode

> varMetadata(transbig)$labelDescription <- c("Age",

+ "tumour size", "tumour grade", "Estrogen receptor status",

+ "relapse free survival time", "relapse free events",

+ "overall survival time", "overall survival events",

+ "distant metastasis free survival time",

+ "distant metastasis events")

> varMetadata(transbig)

labelDescription

age Age

size.cm. tumour size

grade tumour grade


t.rfs relapse free survival time

e.rfs relapse free events

t.os overall survival time

e.os overall survival events

t.dmfs distant metastasis free survival time

e.dmfs distant metastasis events

This completes the Wang ExpressionSet

> validObject(transbig)

[1] TRUE

> transbig




phenoData

sampleNames: GSM177885, GSM177886, ..., GSM178082 (198 total)

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age: Age

size.cm.: tumour size

...: ...

e.dmfs: distant metastasis events

(10 total)

featureData

featureNames: 1007_s_at, 1053_at, ..., AFFX-TrpnX-M_at (22283 total)


probeID: Affymetrix probe identifier

symbol: gene symbol

...: ...


(6 total)


2.4 Natrajan dataset

The gene expression data of the cohort of 53 grade III invasive ductal carci-nomas published by Natrajan et al (7) are publicly available at ArrayExpress(E-TABM-543). Expression data from the Illumina Human WG6 v2 array wasprocessed with BeadStudio software and pre-processed in R using the lumi pack-age version 1.8.3. Data was read using lumiR without background subtractionand subjected successively to variance stabilisation transformation (VST) androbust spline normalisation (RSN).

Gene expression data and phenoData can be loaded into an ExpressionSet ”Na-trajan” with the code

> Natrajan <- readExpressionSet(exprsFile = "http://rock.icr.ac.uk/

collaborations/Mackay/centroid.correlations.Eset/natrajan.exprs.txt",


collaborations/Mackay/centroid.correlations.Eset/natrajan.pdata.txt",


+ na.strings = c("", "NA", "N/A"), row.names = 1)

Annotation of the Natrajan dataset was based upon Illumina BeadStudio an-notation, annotation using the R annotation library ”lumiHumanAll.db” (1.6.1)and ensembl annotation retrieved from Biomart based upon the ILMN Illuminatranscript identifier. FeatureData of the Natrajan ExpressionSet is annotatedwith the unique nuID identifier as described in the lumi package, the gene sym-bol and description supplied by BeadStudio, the Genbank accession number andthe ensembl gene identifier retrieved from Biomart based upon NCBI build 36and ensembl assembly 54.

FeatureData annotation of the Natrajan dataset can be read with the code

> Natrajan.fdata <- read.delim("http://rock.icr.ac.uk/

collaborations/Mackay/centroid.correlations.Eset/natrajan.fdata.txt",



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All probeIDs in the featureData file match those in the Natrajan ExpressionSet

> all(Natrajan.fdata$nuID == featureNames(Natrajan))

[1] TRUE

FeatureData of the Natrajan ExpressionSet is annotated with the code

> featureData(Natrajan)$nuID <- Natrajan.fdata$nuID

> featureData(Natrajan)$symbol <- Natrajan.fdata$symbol

> featureData(Natrajan)$description <- Natrajan.fdata$description

> featureData(Natrajan)$accession <- Natrajan.fdata$accession

> featureData(Natrajan)$ensg <- Natrajan.fdata$ensg

Since multiple Unigene cluster identifiers annotate many of the Illumina V2probes, Unigene cluster IDs were selected which are present in the annotationof published breast cancer centroids and separately annotated in the NatrajanExpressionSet.

> featureData(Natrajan)$Sorlie500.unigene <- Natrajan.fdata$Sorlie500.unigene

> featureData(Natrajan)$Hu306.unigene <- Natrajan.fdata$Hu306.unigene

> featureData(Natrajan)$PAM50.unigene <- Natrajan.fdata$PAM50.unigene

MetaData was added to describe the feature Data annotation in the NatrajanExpressionSet with the code

> fvarMetadata(Natrajan)$labelDescription <- c("nuID unique identifier",

+ "gene symbol", "gene description", "accession number",

+ "ensembl gene ID", "unigene cluster IDs - Sorlie 500",

+ "unigene cluster IDs - Hu 306", "unigene cluster IDs - PAM 50")

> fvarMetadata(Natrajan)

labelDescription

nuID nuID unique identifier

symbol gene symbol




Sorlie500.unigene unigene cluster IDs - Sorlie 500

Hu306.unigene unigene cluster IDs - Hu 306

PAM50.unigene unigene cluster IDs - PAM 50

MetaData was added to describe the phenoData in the Natrajan dataset.

> varMetadata(Natrajan)$labelDescription <- c(

+ "HER2 amplification status", "ER status",

+ "PR status", "Nodal status", "Tumour size")

> varMetadata(Natrajan)

labelDescription

HER2 HER2 amplification status

ER ER status

PR PR status

node Nodal status

size Tumour size

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This completes the Natrajan ExpressionSet

> validObject(Natrajan)

[1] TRUE

> Natrajan




phenoData

sampleNames: B1, B11, ..., B9 (53 total)


HER2: HER2 amplification status

ER: ER status

...: ...

size: Tumour size

(5 total)

featureData

featureNames: 9g8cQB1TZtuiix.ulU, fJUdX0IAn_P9VLTgJU, ..., xopB7pPn1

8FJ067uDs (48701 total)


nuID: nuID unique identifier

symbol: gene symbol

...: ...

PAM50.unigene: unigene cluster IDs - PAM 50

(8 total)


3 Centering Gene Expression values

Gene expression values in each dataset were centered with the following codechunk which uses the NKI295 ExpressionSet as an example

> NKI295.centered <- NKI295

> exprs(NKI295.centered) <- t(scale(t(exprs(NKI295)),

+ center = apply(t(exprs(NKI295)),

+ 2, median, na.rm = T), scale = F))

Centroid correlations from un-centered data were removed from phenoData withthe code

> pData(NKI295.centered) <- pData(NKI295.centered)[, -grep("centroid",

+ varLabels(NKI295.centered))]

4 Combining average expression of probes car-rying the same annotation

To investigate the combination of multiple probes representing the same geneon each platform, the average gene expression from probes carrying the same

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annotation was combined with the code

> NKI295.symbol <- NKI295[!is.na(fData(NKI295)$symbol), ]

> new.exprs <- split(exprs(NKI295.symbol), fData(NKI295.symbol)$symbol)

> new.exprs <- lapply(new.exprs, FUN = function(x) {

+ matrix(x, ncol = ncol(NKI295.symbol))})

> new.exprs <- lapply(new.exprs, colMeans, na.rm = T)

> new.exprs <- matrix(unlist(new.exprs), nrow = length(new.exprs),

+ ncol = ncol(NKI295.symbol))

> row.names(new.exprs) <- featureNames(NKI295.symbol)

+ [!duplicated(fData(NKI295.symbol)$symbol)]

> NKI295.symbol.average <- NKI295.symbol

+ [!duplicated(fData(NKI295.symbol)$symbol), ]

> exprs(NKI295.symbol.average) <- new.exprs

Centroid correlations from original data were removed from phenoData with thecode

> pData(NKI295.symbol.average) <- pData(NKI295.symbol.average)

+ [, -grep("centroid", varLabels(NKI295.symbol.average))]

5 Centroid Correlations

Annotated centroids and ExpressionSet objects can now be combined to per-form centroid correlations. Centroid correlations are performed with a single Rfunction ”centroidCorrelation”.

The function ”centroidCorrelation” takes the following as its arguments

eset- the ExpressionSetcentroid- the annotated centroid data framecentroids- the number of centroids (phenotypic groups)centroid.id- the gene identifier in the centroid annotationeset.id- the featureData identifier in the ExpressionSetproject- a project string with which to label output filescor.method- the correlation method (pearson/spearman) to usereturn.eset- a logical call to return the ExpressionSetpheno.label- a label for Nearest centroid in the ExpressionSet phenoDatareturn.exprs- write out the expression values for matching probes

The function is written to perform a series of straightforward correlations ofgene expression values with published centroids for gene expression, to recordthe centroid with the highest correlation ”the nearest centroid”, to write theresults of the correlation into ExpressionSet objects and to write the centroidcorrelations into a results file combined with the ExpressionSet phenoData. cen-troidCorrelation is based upon the overlay of identifiers carried in the annotatedcentroids data frame and the ExpressinSet featureData. For example if ”symbol”is specified as the eset.id and the centroid.id, this annotation column in the cen-troid and the ExpressionSet featureData is used to subset the centroid and the

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ExpressionSet to those features which are common to both. If present, dupli-cated identifiers are removed to keep only the probes with the highest variancecarrying each identifier and the number of matched probes is returned to thecommand line. Once the intersection between the centroid data frame and theExpressionSet has been established, the correlations are run using the specifiedcorrelation method and the results recorded in the output. The nearest centroidis recorded for every sample and those with an absolute correlation of less than0.1 are filtered out. This ”nearest centroid” is recorded in the ExpressionSetphenoData for each sample under the specified label.

Source the centroidCorrelation function with the code

> source("http://rock.icr.ac.uk/collaborations/Mackay/

centroid.correlations.Eset/centroidCorrelationEset.R")

The centroidCorrelation function can then be run with the code

> NKI295 <- centroidCorrelation(NKI295, Sorlie.centroids,

+ centroids = 5, centroid.id = "symbol", eset.id = "symbol",

+ project = "NKI295.Sorlie500.pearson.symbol.testing",

+ cor.method = "pearson",

+ pheno.label = "Sorlie500.symbol.pearson.nearest.centroid")

396 matching identifiers

> NKI295 <- centroidCorrelation(NKI295, Sorlie.centroids,


+ project = "NKI295.Sorlie500.spearman.symbol",

+ cor.method = "spearman",

+ pheno.label = "Sorlie500.symbol.spearman.nearest.centroid")


> NKI295 <- centroidCorrelation(NKI295, Hu.centroids, centroids = 5,

+ centroid.id = "symbol", eset.id = "symbol",

+ project = "NKI295.Hu.306.spearman.symbol",


+ pheno.label = "Hu306.symbol.spearman.nearest.centroid")


> NKI295 <- centroidCorrelation(NKI295, PAM50.centroids,


+ project = "NKI295.PAM50.spearman.symbol",


+ pheno.label = "PAM50.symbol.spearman.nearest.centroid")


This function will write create a results directory called ”centroid correlations”in your R working directory and write results files called (for example)NKI295.PAM50.spearman.symbol.nearest.centroids.xls.The file records the correlations of each sample to each of the centroids combined

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with the phenoData of the input ExpressionSet object. In the code chunk abovecentroidCorrelation records nearest centroids under the specified label in thephenoData of the ExpressionSet NKI295 which can be seen with the code below

> varLabels(NKI295)

[1] "Label_Traing_and_Validation"

[2] "event_death"

[3] "Distant_metastasis_as_first_event.MCR."

[4] "survival.death."

[5] "timerecu.MCR."

[6] "diameter.mm."

[7] "size"

[8] "node"

[9] "grade"

[10] "ER"

[11] "Age.years."

[12] "X70_genes"

[13] "Sorlie_Corr_5"

[14] "Sorlie_cor_CutOff_0.1"

[15] "Cor.Normal"

[16] "Cor.ERBB2"

[17] "Cor.LumA"

[18] "Cor.LumB"

[19] "Cor.Basal"

[20] "Fan.nearest.centroid"

[21] "Sorlie500.symbol.pearson.nearest.centroid"

[22] "Sorlie500.symbol.spearman.nearest.centroid"

[23] "Hu306.symbol.spearman.nearest.centroid"

[24] "PAM50.symbol.spearman.nearest.centroid"

> head(data.frame(sampleNames = sampleNames(NKI295),

+ Sorlie500 = pData(NKI295)$Sorlie500.symbol.spearman.nearest.centroid,

+ Hu306 = pData(NKI295)$Hu306.symbol.spearman.nearest.centroid,

+ PAM50 = pData(NKI295)$PAM50.symbol.spearman.nearest.centroid), 10)

sampleNames Sorlie500 Hu306 PAM50

1 NKI295_4 LuminalB LuminalB

2 NKI295_6 LuminalA LuminalA LuminalA

3 NKI295_7 Normal Normal Normal

4 NKI295_8 Basal Basal Basal

5 NKI295_9 LuminalA LuminalA

6 NKI295_11 LuminalB HER2 HER2

7 NKI295_12 Basal Basal Basal

8 NKI295_13 LuminalB HER2

9 NKI295_14 LuminalA LuminalA LuminalA

10 NKI295_17 Normal LuminalA LuminalA

For each dataset centroid correlations were performed using the 3 publishedcentroids described by Sorlie (1), Hu (2) and Parker (3). Spearman rank corre-lations were performed for each and Pearson correlations were performed only

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for the Sorlie centroids. For each dataset centroid correlations were performedon all probes with and without centering and on the combined average of probescarrying the same gene symbol, Unigene clusterID and ensembl gene ID withand without centering.A complete R history of all the centroid correlations performed in Weigelt et alis available athttp://rock.icr.ac.uk/collaborations/Mackay/centroid.correlations.Eset/

6 References

1. Sorlie T, Tibshirani R, Parker J, et al. Repeated observation of breast tumorsubtypes in independent gene expression data sets.Proc Natl Acad Sci U S A 2003;100(14):8418-23.2. Hu Z, Fan C, Oh DS, et al. The molecular portraits of breast tumors areconserved across microarray platforms.BMC Genomics 2006;7:96.3. Parker JS, Mullins M, Cheang MC, et al. Supervised risk predictor of breastcancer based on intrinsic subtypes.J Clin Oncol 2009;27(8):1160-7.4. van de Vijver MJ, He YD, van’t Veer LJ, et al. A gene-expression signatureas a predictor of survival in breast cancer.N Engl J Med 2002;347(25):1999-2009.5. Wang Y, Klijn JG, Zhang Y, et al. Gene-expression profiles to predict distantmetastasis of lymph-node-negative primary breast cancer.Lancet 2005;365(9460):671-9.6. Desmedt C, Piette F, Loi S, et al. Strong time dependence of the 76-geneprognostic signature for node-negative breast cancer patients in the TRANSBIGmulticenter independent validation series.Clin Cancer Res 2007;13(11):3207-14.7. Natrajan R, Weigelt B, Mackay A, et al. An integrative genomic and tran-scriptomic analysis reveals molecular pathways and networks regulated by copynumber aberrations in basal-like, HER2 and luminal cancers.Breast Cancer Res Treat 2009:epub ahead of print.

7 Data repository

All data used in this analysis is archived in the web supplement to Weigelt etal. http://rock.icr.ac.uk/collaborations/Mackay/centroid.correlations.Eset/

8 Contact Information

For questions or comments on the data contained within this analysis, the meth-ods used or further help to reproduce the analyses please contact Alan [email protected].

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Documents

Weigelt et al - SupplementaryMethods - Re-Revised-clean · ‘centroids’ for each SSP included in this study ... updated Unigene cluster IDs were used to annotate each centroid/SSP