San Antonio Breast Cancer Symposium Highlights … Antonio Breast Cancer Symposium Highlights 2016 ... –Known to drive breast cancer risk vs. minimal information ... and hypofractionated

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San Antonio Breast Cancer Symposium Highlights 2016

A Surgeon’s Perspective

Candice Sauder M.D., M.Ed.Department of Surgery

Division of Surgical OncologyUC Davis

Overview• Genetic Risk and Guidelines

– S2-01– ASBS Consensus Guideline on Hereditary Genetic Testing

• Genetic Risk and Breast Cancer Outcomes– S2-03

• Ductal Carcinoma In Situ– SSS-ASTRO-ASCO DCIS Margin Guidelines– S5-01– P1-11-03

• Staging the Regional Axilla after NCT– S2-07– P6-09-01– OT2-03-01– Alliance 11202

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Genetic Risk and Guidelines• Last 4 years drastic changes in the field of cancer

genetics– Particularly this field now contains genetic panels that can

have up to 50 genes

• What genes were included?– Known to drive breast cancer risk vs. minimal information

but a possibility of involvement

• How do we handle giving a clinical risk estimate with the wide conference intervals seen on many of these genes?

• What does a VUS mean for our patients?

Genetic Risk and Guidelines

Fergus Crouch in S2-01 summarizing Doug Eastman et al. NEJM. 2015.

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Genetic Risk and GuidelinesBreast cancer risks associated with mutations in cancer predisposition genes identified by clinical genetic testing of 60,000 breast cancer patients

Couch FJ, Hu C, Lilyquist J, Shimelis H, Akinhanmi M, Na J, Polley EC, Hart SN, McFarland R, LaDuca H, Huether R, Goldgar DE, Dolinsky JS (S2-01)

121,197 patients examined from the Ambry Genetics database from March 2012-June 2016

– 92.4% female

– 65% Caucasian

Mutations were detected in 9% of patients

12 genes showed a significant association with breast cancer

Genetic Risk and GuidelinesHighRisk BRCA1

BRCA2TP53PTENCDH1PALB2

ModerateRisk

ATMCHEK2RAD51DNF1BARD1MSH6

LowRisk BRIP1RAD50RAD51cMRE11ANBN

http://discoverysedge.mayo.edu/2015/10/07/breast-cancer-predicting-individual-risk

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Genetic Risk and GuidelinesASBSConsensusGuidelinesonHereditaryGeneticTesting

BRCA1 Breastcancer(upto67%)Contralateralbr cancer(upto30%)Ovariancancer(upto45%)

AnnualbreastMRI(startage25)Annualmammogram(startage30)Risk-reducingbilateralmastectomy

BRCA2 Breastcancer(upto66%)Contralateralbr cancer(upto30%)Ovariancancer(upto12%)MalebreastcancerProstatecancer

AnnualbreastMRI(startage25)Annualmammogram(startage30)ChemopreventionRisk-reducingbilateralmastectomy

TP53 BreastcancerSofttissuesarcomasOsteosarcomasBraintumorsAdrenocorticalcarcinomaMultipleprimarytumors



PALB2 Breastcancer(33%,but58%with2first-degreerelatives)PancreaticcancerMalebreast


CDH1 Breastcancer(39%oflobularcarcinoma)GastriccancerColorectalcancer

AnnualbreastMRI(startage30)Annualmammogram(startage30)Risk-reducingbilateralmastectomyGastricscreening

PTEN BreastcancerThyroidcancerEndometrialcancerColorectalcancerKidneycancer


ATM Breastcancer(raremutationswitha40-60%)

Managementrecommendationshavenotbeenestablished

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CHEK2 Breastcancer(20%butincreaseswith44%with1st- &2nd-degreerelatives)30%riskofcontralateralbreastcancerMalebreastcancerColoncancerProstatecancerThyroidcancerKidneycancer

MRIChemopreventionRisk-reducingbilateralmastectomy

STK-11 BreastcancerOvariancancerColorectalcancerDuodenalcancerPancreaticcancer

AnnualbreastMRI(startage30)Annualmammogram(startage30)

BRIP1 Breastcancer(2- to3.5-fold)Ovariancancer(8-fold)

MRIChemopreventionConsiderBSO

Genetic Risk & Breast Cancer Outcomes

Does BRCA status affect outcome in young breast cancer patients? Results from the

prospective study of outcomes in sporadic and hereditary breast cancer (POSH)

Eccles DM, Copson ER, Maishman T, Tapper W, Cutress R, Gerty S, Stanton L, Altman DG, Durcan L, Simmonds P, Decker B, Allen J, Luccarini C, Easton D, Dunning A (S2-03)

3053 patients examined from the UK 2000-2008– All had Invasive Breast Cancer

– ≤ 40 years old

Blood samples were tested for BRCA1 & 2 in 2016

Mutations were found in 379/2759 (~14%)

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Genetic Risk & Breast Cancer Outcomes

Looked at the molecular subgroups– TNBC survival favored BRCA gene carriers (~11% at 10

years)

Ductal Carcinoma In SituSociety of Surgical Oncology–American Society for Radiation Oncology–American Society of Clinical

Oncology Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in

Ductal Carcinoma In SituMonica Morrow, Kimberly J. Van Zee, Lawrence J. Solin, Nehmat Houssami, Mariana Chavez-MacGregor, Jay

R. Harris, Janet Horton, Shelley Hwang, Peggy L. Johnson, M. Luke Marinovich, Stuart J. Schnitt, Irene Wapnir, and Meena S. Moran

Literature review which included 20 studies of 7883 women

2mm margins were adequate– Larger margins did not decrease the RR

– Positive margins have a much higher RR

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Ductal Carcinoma In Situ• Treatment with surgery alone is linked to a higher

RR compared to treatment with surgery and WBRT.

• Treatment with HT can reduce the RR, but no data has shown a link between HT and the width of clean margins.

• The width of the clean margins shouldn’t affect the type of WBRT a woman receives.

• DCIS with microinvasion should be considered DCIS when deciding on optimal margin width.

Ductal Carcinoma In SituDCIS biological risk profile predicts risk of

recurrence after breast conserving surgery in a Kaiser Permanente NW population

Bremer T, Whitworth P, Leo M, Barry T, Goldstein N, Ganders C, Francisco M, Leesman G, Linke S, Patel R, Pellicane J, Weinmann S. (S5-01)

Validation study of a new prognostic indicator – 0-10 (Low ≤3, High >3)

– Goal to identify the 72% that are not helped by RT

Correa et al. Natl Cancer Inst Monographs. 2010

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Ductal Carcinoma In Situ

10yearIBERisk

RTN=377

DCISBCS(1990-2007)

N=608

ProspectiveBiologicalRiskSignatureTestingN=455

NoRTN=78

Ductal Carcinoma In Situ

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Ductal Carcinoma In SituRates of ipsilateral breast tumor recurrence (IBTR) following breast concerving surgery

(BCS) and hypofractionated radiotherapy for ductal carcinoma in situ (DCIS)

Dumitru D, Benson J, Wishart G, Provenzano E. (P1-11-03)

15 fractions for 40Gy

Ductal Carcinoma In Situ• 8.3% developed recurrence (n=9 with RT and

n=5 no RT, p=0.534) at 10.5 years

• Similar IBTR rates seen in with Traditional WBRT (approx. 1% per year)

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Staging the Regional Axilla after NCT

• Degree of pathologic response after NCT correlates with both DFS and OS in both the breast and axilla

• Likelihood of pCR is predicted by molecular subtype

• Overall pCR is a prognostic factor, which differs slightly by molecular subtype

Total ~40%

ER/PR+ 21.1%

Her-2 + 64.7%

TripleNegative 49.4%Boughey JC et al. Ann Surg 2014.

Dominici et al. Cancer. 2010.Bear et al. JCO. 2003.


Predictors of locoregional recurrence after neoadjuvant chemotherapy and

surgery for node positive breast cancer: Results from ACOSOG Z1071 (Alliance)

Boughey JC, Ballman KV, McCall LM, Mittendorf EA, Hunt KK (P6-09-01)

5 year LRR

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ClinicallyNegativeAxilla

NCT SLNB


Sentinel node detection after neoadjuvant chemotherapy in patient without previous axillary node involvement (GANEA 2 trial):

Follow-up of a prospective multi-institutional cohort

Classe J-M, Loaec C, Alran S, Paillocher N, Tunon-Lara C, Gimbergues P, Faure-Virelizier C, Chauvet M-P, Lasry S, Dupre P-F, Verhaeghe J-L, De Blaye P, Gutowski M, Barranger E, Lecuru F, Lefevre Lacoeuille C,

Loussert L, Lambaudie E, Ferron G (S2-07)

Useful, feasible, safe– 92.4% female

– 65% Caucasian

Cohort of 15 Institutions

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SLNB+ALNDn=307

79.8%identifiedFNR~20%

T1-4BrCaAxUltrasound

N=608

+SLN24%N=139

+LN - LNSLNB± ALND

n=50997%identified

- SLN75%

ALNDpN-=73%(n=88)pN+=24%

(Mi=12Macro=15)

SLNBaloneN=418

ALNDN=14


3yearsurvival N=418

OverallSurvival 97.8%

DiseaseFreeSurvival 94.8%

Recurrence N=10

Metastasis 3

IpsilateralBreast 3

ContralateralBreast 3

LymphNode 1

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ClinicallyNegativeAxilla

ClinicallyPositiveAxilla

NCT

NCT

SLNB

ALND

Complete Response

No Complete Response

?

Staging the Regional Axilla after NCTPredictor of LRR after NCT in NSABP B-18 & B-27

cN-/ypN+

cN+/ypN+

E. Mamounas. JCO. 2012

cN-/ypN-

cN+/ypN-

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Staging the Regional Axilla after NCTACOSOG (Alliance) z1071 Trial

FNR12.6%Goal10%

NCT

T1-4,N1-2,M0WithBx provenLNdisease

N=663

SLNIDed (≤2),thenfollowedwithALNDN=525(79%)

J. Boughey et al. JAMA. 2013


ACOSOG (Alliance) z1071 Trial

J. Boughey et al. JAMA. 2013

NumberofSLNRemoved 1 2 ≥3FalseNegativeRate 32% 21.1% 9.1%Total 12.6%

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Targeted Axillary Lymph Node Dissection (TAD)

A Caudle et al. JCO. 2016

Node +LN TotalLN FNR

Clipped 115 120 4.2%

SLNB 62 69 10.1%

SLNB+Clipped 73 74 1.4%


• Normal Exam after chemotherapy– ± axillary imaging

• Remove ≥ 3LNs

• Dual Mapping

• Remove Targeted/Clipped Node

• Count all remaining disease as a positive node– Even IHC detected (FNR 8.4%)

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NSABP B-51/RTOG 1304 (NRG 9353)

Poster OT2-03-01

Alliance for Clinical Trials in Oncology A11202

King, T. A. & Morrow, M. “Surgical issues in patients with breast cancer receiving neoadjuvant chemotherapy.” Nat. Rev. Clin. Oncol. 2015.

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Thank You.

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San Antonio Breast Cancer Symposium Highlights … Antonio Breast Cancer Symposium Highlights 2016 ... –Known to drive breast cancer risk vs. minimal information ... and hypofractionated