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Moderne mammadiagnostikk –
hvor står vi og hvor går vi ?
25 min.
Professor dr.med. emeritus Per Skaane
Oslo University Hospital Ullevaal
Breast Imaging Center
Oslo / Norway
NBCG Oslo 15. juni 2018
• Conventional mammography:
- Screen-film mammography (SFM)
- Xeromammography
- Computed radiography CR (CR-mammo)
- Full-field digital mammography (FFDM)
- Standard views (cc, mlo, lat)
- Supplemental views (mag - cone view)
- Ductography (galactography) (today:MRI!)
- Mammography-guided biopsy
• Advanced mammographic techniques:
- Digital breast tomosynthesis (DBT)
- Contrast-enhanced spectral mammography (CESM)
Mammographic techniques *
* Projection images using X-ray (i.e., «MR mammography», «Ultrasound mammography»
«Dedicated breast CT» and other modalities should not be
included in «mammographic techniques»!)
• Conventional mammography
• - incl. supplemental views, mx-guided biopsy
• Ultrasonography
• - (Doppler imaging)
• - (Elastography)
• - US-guided biopsy
• MRI
• - incl. several sequences (T1, T2, CE-MRI, DWI)
• - MRI-guided biopsy
Today:
Assessment of palpable and non-palpable breast abnormalities
A) Klinisk mamma-diagnostikk : Hvor står vi og Hvor går vi ?
• Mammography
- incl. supplemental views, mx-guided biopsy
- Advanced mammographic techniques:
- Digital breast tomosynthesis (DBT)
- Contrast-enhanced spectral mammography (CESM)
- Spectral imaging (mammography)
• Ultrasonography
- Conventional B-mode
- Doppler imaging plus advanced techniques
• MRI
- incl. several sequences (T1, T2, CE-MRI, DWI)
- «ABB-MRI» (screening?!)
• Isotope scanning (molecular breast imaging - PEM)
• Diffuse Optical Tomography (DOT)
• Computed tomography (dedicated breast CT)
• Fusion (hybrid) techniques (FDG-PET and others)
Tomorrow:
Assessment of palpable and non-palpable breast abnormalities
DBT System by
Manufacturer
Scan angle Range, 15 - 50 º
Pixel size Range, 50 – 100 µ
Projections Range, 9 - 25
Scan time Range, 4 - 25 s
Tube motion - Step-and-shoot
- Continuous
Reconstruct. FBP / Iterative
FBP: Filtered back projection
Overlapping structures (cancer) can hide in 2D, but are clearly seen in a DBT (3D) slice
Digital Breast Tomosynthesis (DBT)
Preibsch H: Radiologe 2015;55:59-69
Contrast-enhanced mammography:
a) Temporal Subtraction Approach
Works in Progress. Not cleared by
the FDA for use in the US.
Non-ionic contrast
agent injected into the patient
Mask
image
taken
Several Post-contrast
images taken at certain
time intervals
time
(Post-contrast
image at 5-min) –
(Mask image)
Log Subtraction:
(Each Post-contrast
image) – (Mast image)
(1) (2) (3) (4) (5)
Mask
Image
time
Contrast
uptake
Uptake and Washout
of Cancer
Images Courtesy of Martin Yaffe PhD, Sunnybrook
b) Dual Energy Subtraction Approach
( Dual-energy: Contrast-Enhanced Spectral Mammography CESM )
Eur J Radiol 2015
a)
Spectral mammography
(«spectral imaging»): Is it possible to distinguish cysts from
tumors on screening mammograms ?
Left: Philips MicroDose Mammography system
Right: The spectral image receptor and electronics
The Philips MicroDose Mammography system
Cases where LCT works
CIST_00084: Cyst
Pcyst = 70%
Slide courtesy: Sectra - Philips, Stockholm
Breast US
Primary tumor features :
• Shape
• Axial orientation
• Contour (margin)
• Echotexture
• Echogenicity
• Transmission
• Surrounding
Skaane P et al.: Am J Roentgenol 1998;170:109
Advanced applications :
• Higher frequencies
• Color Doppler
• Power Doppler
• Compound scanning
• Harmonic imaging
• Contrast-enhanced US
• Increased specificity («down-grading»)
• Influence on decision making ?
98%
AngioPLUS
Jung HK et al.
B-mode PDI
«ROC (AUC) showed that AngioPLUS was superior to power Doppler US in
differentiating benign from malignant breast masses, but the difference was
not statistically significant»
Park AY et al.
B-mode US CDI PDI SMI
MacDonald L: J Nucl Med 2009;50:1666
Computed tomography:
Dedicated breast CT
O’Connell A et al.: AJR 2010;195:496
Canon cone beam breast CT skanner:
X-ray tube rotates 360 degrees around
the breast (placed into a cup);
not regulated for commercial use.
Combined optical and tomosynthesis imaging
Invasive ductal carcinoma 25 mm
Hybrid techniques:
Work in progress (experimental): Dual-Modality Tomosynthesis (DMT)
Fang Q et al.: Radiology 2011;258:89-97
Hybrid scanning: Tomosynthesis
and 99m sestamibi gamma imaging
Williams MB et al.: Radiology 2010;255:181
Morphological («qualitative») imaging tests: «Conventional imaging» such as mammography, US, DBT Functional («quantitative») imaging techniques: «Advanced imaging» such as MRI, CESM, PET/CT
A) PET/MRI: Complete response after NAC
B) PET/MRI: Incomplete response after NAC
Pretreatment After 1. NAC cycle
Pretreatment MRI MRI after 1. NAC cycle
Preop. MRI after 8 NAC cycle: No enhancement; histo: No residual tumor
Pretreatment After 1. NAC cycle
Pretreatment MRI MRI after 1. NAC cycle
Preop. MRI after 8 NAC cycle: Enhancing mass; histo: 3.6-cm IDC grade 3
Cho N et al.
Bassett LW et a.: Diagnosis of Diseases of the Breast. Elsevier Saunders, 2005
JAMA 1961
B) Mammografi – screening: Hvor står vi og Hvor går vi ?
Conventional mammography has two serious inherent limitations:
1. Low sensitivity
(cancer detection rate)
in women with dense
breast parenchyma due
to superimposed tissue
(“masking effect”)
2. Low specificity (false positive interpretations) due to summation of
normal parenchyma (“pseudotumors”)
0
10
20
30
40
50
60
70
80
90
100
I II II IV
BI - RADS Density
Sen
sit
ivit
y
Mammography:
Sensitivity (%) and breast density
BI-RADS (ACR) density category 1 – 4
The «gold standard» of breast cancer screening today is conventional
Full-Field Digital Mammography (FFDM)
Breast cancer screening in the future might require a better diagnostic test !
Multifocal invasive ductal carcinoma (IDC)
Screening:
CE: Lump + (?)
MX neg / US neg / FNAC neg
Breast MRI: The highest sensitivity for breast cancer
Hall FH
The Rise and Impending Decline of Screening Mammography
Radiology 2008; 247: 597-601:
”I believe that mammography is going to be replaced by
magnetic resonance (MR) imaging, not only in high-risk
women but increasingly in those at average risk.”
However:
Two main challenges (problems) regarding implementation of «ABB-MRI»
for women at average risk in population-based screening remain:
1.Costs
2.Availability
Acquisition time of «Abb-MRI» (and «Short first-pass MRI» of the breast)
is only about 3 to 4 minutes – and reading time for MIP images very short
• A) DBT – pros:
• Reduced summation simulating masses («pseudotumors»)
(i.e., increased specificity and lower recall rates)
• Replacement of supplemental views for non-calcified lesions
(i.e., increased specificity and lower recall rates)
•Increased cancer conspicuity and visibility
(i.e., increased cancer detection rates)
• B) DBT – cons («challenges»):
• One- vs. two-view DBT, radiation dose, and synthetic 2D
• Microcalcifications: syn2D and DBT vs. FFDM
• The (very) dense breast
• Lesions seen only on DBT («tomo-only lesions»)
• Increased work-load / interpretation time
• Overdiagnosis («length-time bias»)
• Cost-effectiveness
Tomosynthesis (DBT) in breast cancer screening: Pros and «Cons»
Indeterminate / suspicious
finding on FFDM
A) Excluding the presence of a mass
B) Confirming the presence of a benign mass
Lcc: Syn2D
?
Lcc: DBT
DBT – pros: Increased specificity (reduced recall rate)
Circumscribed mass: Cyst or tumor ? Ultrasound !
Replacement of supplementary mammographic views for non-calcified lesions
?
Lcc: FFDM (2D)
? ?
Assessment: Lcc 1. and 2. cone-mag views
Lcc: 3D (Tomo)
DBT – pros in breast cancer screening:
OTST: IDC G2, 4.5 mm
FFDM R mlo TOMO R mlo
FFDM R cc TOMO R cc
IDC G2, 14mm (+ DCIS G3, 24 mm)
Tubular carcinoma 6 mm
DBT – pros: Increased cancer conspicuity and visibility (i.e., increased sensitivity)
a) Increased cancer conspicuity
b) Increased cancer visibility
Study Popul - 2D
- 3D
Recall % Sign
CDR n Sign
Yale Uni, New Haven, CT 2D
Haas BM: Radiology 2013 3D
7058
6100
12.0
8.4
5.2
5.7
TOPS, Houston, TX
Rose SL: AJR 2013
13856
9499
8.7
5.5
4.0
5.4
US Comm. Practice, MD-VA
Greenberg JS: AJR 2014
38674
20943
16.2
13.6
4.9
6.3
E. Wende Breast Care, NY
Destounis S: J Clin Imag Sci 2014
524
524
11.5
4.2 NA
Pennsylvania, Philadelphia, PA
McCarthy AM: JNCI 2014
10728
15571
10.4
8.8
4.6
5.5
Yale Uni, New Haven, CT
Durand MA: Radiology 2015
9364
8591
12.3
7.8
5.7
5.9
Brown Uni, Providence, RI
Lourenco AP: Radiology 2015
12577
12921
9.3
6.4
5.4
4.6
US multicenter study
Friedewald SM: JAMA 2014
281187
173663
10.7
9.1
4.2
5.4
Harvard Med Sch, Boston, MA
Sharpe RE: Radiology 2016
70173
5587
7.5
6.1
3.5
5.4
Pennsylvania, Philadelphia, PA
McDonald ES: AJR 2015
9524
13712
9.1
7.8
4.6
5.4
Significant
Retrospective US screening studies comparing 2D+3D (FFDM+DBT) vs. 2D (FFDM) alone
Study Popul - 2D
- 3D
Recall % Sign
CDR n Sign
Newark, DE, USA 2D
Aujero MP: Radiology 2017 3D
32076
30561
8.7
5.8
5.3
6.4
PROSPR consortium, US
Conant EF: BCRT 2016
142883
55998
10.4
8.7
4.4
5.9
Uni Utah, Salt Lake City, UT
Freer PE: BCRT 2017
21435
1019
8.7
7.0
5.9
6.9
Dpt. Radiology, Brigham, MA
Giess CS: AJR 2017
16264
21074
10.3
10.7
1.8
3.8
Pennsylvania, Philadelphia, PA
McDonald ES: JAMA Onc 2016*
10728
11007
10.4
8.8
4.6
5.5
Ohio State Uni, Columbus, OH
Powell JL: Acad Radiol 2016
10477
2304
16.2
13.8
5.2
7.8
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
FFDM: Full-Field Digital Mammography
DBT: Digital Breast Tomosynthesis
Popul: Study population
CDR: Cancer Detection Rate
ns: Non-significant
NA: Non applicable (not given)
* Year 1 DBT cohort
Study Design Reading Population
( n ) Recall: (%) Difference
Cancer
detection*
Cancer
increase
STORM
(Italy) 1)
Prosp.
paired
Double
sequent.
2D: 7,292
3D: 7,292
2D: 5.2
3D: 4.3 a - 17%
5.3
8.1 + 51%
OTST
(Norway) 2)
Prosp.
paired
Double
parallel
2D: 12,621
3D: 12,621
2D: 10.3
3D: 8.5 b - 18%
7.1
9.4 + 34%
MBTST
(Sweden) 3)
Prosp.
paired
Double
sequent.
2D: 7,500
3D: 7,500
2D: 2.6
3D: 3.8 c + 43%
6.3
8.9 + 43%
STORM-2
(Italy) 4)
Prosp.
paired
Double
sequent.
2D: 9,677
3D: 9,677
2D: 3.4
3D: 4.0 d + 13%
6.3
8.5 + 34%
Cordoba
(Spain) 5)
Prosp.
paired
Double
Sequent.
2D: 16,067
3D: 16,067**
2D: 5.0
3D: 4.4 e - 13%
4.7
5.7 + 17%
OTST
(Norway) 6)
Prosp.
historical
Double
parallel
2D: 59,877
3D: 24,301
2D: 4.2 f
3D: 3.4 - 20%
6.3
9.3 + 47%
OVVV
(Norway) 7)
Prosp.
geographic Double
2D: 61,742
3D: 37,185**
2D: 3.3 g
3D: 3.4 + 3%
6.1
9.4 + 54%
1) STORM (Trento-Verona): Ciatto S et al. Lancet Oncol 2013;14:583 [ a) conditional recall ]
2) OTST (Oslo): Skaane P et al. Eur Radiol 2013;23:2061 [ b) false positive rate ]
3) MBTST (Malmø): Lång K et al. Eur Radiol 2016;26:184 [ c) single-view DBT ]
4) STORM-2 (Trento): Bernardi D et al. Lancet Oncol 2016;17:1105 [ d) results 2D+3D only ]
5) Cordoba (Cordoba): Romero Martin S et al. Eur Radiol 2018; doi [ e) synthetic 2D+DBT ]
6) OTST (Oslo): Skaane P et al. Breast Cancer Res Treat 2018;169:489 [ f) Historical 2D control ]
7) OVVV (Oslo-Drammen-Tønsber): Radiology 2018; doi [ g) Geographical 2D control]
Prospective population-based European studies comparing 2D (FFDM)+3D (DBT) vs 2D alone
* Cancer detection: n / 1000 exams ** syn2D+DBT Significant:
- DBT favour
- DBT disfavour
- ns : non-sign.
ns
Ultrasound: a) Confirming the presence of a mass in the very dense breast
b) Differentiation tumor – cyst if circumscribed mass at DBT
R mlo: FFDM (2D) R mlo: TOMO (3D)
Reader (Arm) A B C D
Score (NBCSP) 1 1 1 2
DBT and the (very) dense breast
Hand-Held US (HHUS)
A) IDC G 2, 15 mm
B) IDC G 1, 4 mm
(screening – high risk woman)
Automated Breast UltraSound (ABUS)
- Images often not reproducible
- Limited documentation
- Comparison with priors difficult
- Time-consuming
- Double reading not possible
- US as stand-alone: low specificity
Limitations of
Hand-Held UltraSonography (HHUS)
in breast cancer screening
Rafferty EA et al.: JAMA 2016;315:1784
In near future: Automated breast density assessment in population-based screening:
Suppl. US screening (single visit) in women with very dense breasts using ABUS !?
ABUS
Images to be included:
One view TOMO (mlo) only?
One view TOMO + one view 2D?
One view TOMO + two view 2D?
Two view TOMO only?
Two view TOMO + one view 2D?
Two view TOMO + two view 2D?
Why do we need 2D (+ TOMO):
2D maximize mc detection?
(TOMO: ”Thin-slice-effect”)
Comparison with prior exams
Comparison right-left breast
Externals may request current 2D
Experience from clinical studies :
Two view 2D (FFDM: MLO + CC) plus two view TOMO (MLO + CC)
seems to offer highest clinical performance .
However: This means a double radiation dose !
Synthetic 2D may substitute for FFDM images
(when combined with tomosynthesis)
without additional radiation dose !!
DBT – challenge: One- vs. two-view DBT, radiation dose, and synthetic 2D
DBT screening: Do we need 2D ?
Invasive lobular carcinoma (ILC) 12 mm, G1 (+ DCIS G3 )
Synthetic 2D image
Rmlo: Conv FFDM (2D) Rmlo: Synthetic 2D Rmlo: Tomo (3D)
Radiology 2017
2006 R MLO: FFDM R MLO: FFDM R MLO: FFDM R MLO:
Synthetic 2D
Screening-detected cancer 2014:
Histology: Radial scar + DCIS G1
* Non-attender 2012
*
Reader score: 1 - 1 Reader score: 1 - 1 Reader score: 1 - 1 Reader score: 5 - 5
2008 2010 2014
Tomosynthesis: «Overdiagnosis» and prevalent DBT screening !
62-year-old-woman
Reader (Arm) 2011 A B C D
Score (NBCSP) 1 1 1 1
TOMO Lcc
20.06.2011
FFDM Lcc
20.06.2011 TOMO Lcc
02.06.2015
FFDM
2011
TOMO
2011
TOMO
2015
2015: Invasive ductal carcinoma
IDC: G2, 15 mm (pT1c, pN1)
Tomosynthesis and detection of early preclinical invasive cancer
Acad Radiol 2015;22:961
«The recent development of tomosynthesis has increased breast cancer
detection while reducing false recalls. Because the greatest harm of
overdiagnosis is overtreatment, the key goal should not be less diagnosis
but better treatment decision tools»
«Overdiagnosis» is an epidemiological concept !
Tomosynthesis screening: « Cost-effectiveness studies «
Of most importance for
healthcare providers and policymakers
Studies confirm that DBT-screening is
cost-effective compared with 2D alone
BUT:
Differences between countries (recalls,
work-up, reimbursement etc.); i.e.;
Each program (country) needs its own analysis !
Today:
« One-size-fits-all » Two-view mammography screening for all
Tomorrow:
« Personalized screening »
Based on:
•Age
•Breast density
•Risk models
•Supplemental imaging techniques / modalities
Improving benefits while reducing harms of breast cancer screening might
require moving from «one-size-fits-all» mammography paradigm
to a «personalized» (individualized) multimodality approach (strategy)
Challenge: Optimize balance between benefit and harms of BC screening:
But: Is «personalized» high-volume (population-based) screening possible ??
Alternatives for supplemental screening Gold standard
Today Tomorrow ?
DBT: The best solution for personalized high-volume (population-based) screening !
Digital Breast Tomosynthesis has the potential to overcome the limitations of
conventional mammography (low specificity and low sensitivity in dense breasts)
Short first-pass MRI: MIP acquired in 4:35 min
Potential improvements of breast cancer screening for women with dense breasts
New techniques / modalities
DBT: A better mammogram !
SFM
FFDM
Tomosynthesis
US
MRI
Tomo
CT
PET
High(er) cost Implementation: Low(er) cost
- New equipment (not CESM) - Existing equipment
- More manpower - Existing manpower
- Re-organization - Existing program
CESM
Thank you very much for your time!
