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EARLY DETECTION: MAMMOGRAPHY

SONOGRAPHY

Elizabeth A. Rafferty, M.D.

Avon Comprehensive Breast Center

Massachusetts General Hospital

Harvard Medical School

Breast Cancer Screening

Early detection of breast cancer is

accomplished through screening.

Screening is undertaken to evaluate an

asymptomatic population in order to

detect unsuspected disease at a time

when cure is still possible.

Screening for breast cancer

• Mammography

• Ultrasound

• MRI

• Mammography

• Ultrasound

• MRI

There is (almost) universal agreement

that the randomized controlled trials of

screening have demonstrated that the

death rate from breast cancer can be

reduced by periodic screening using

mammography.

USPSTF Recommendations

• Against routine screening mammography in women 40-49

• Biennial screening mammography for women 50-74 y.o.

• Insufficient evidence to assess benefits / harms of screening mammography in women > 75 y.o.

• Against teaching BSE

• Insufficient evidence to assess benefits / harms of CBE

• Insufficient evidence to assess benefits / harms of digital mammography or MRI as screening modalities for breast cancer

• Mortality from breast cancer is reduced by

approximately 25 - 30% when introduced in the

population.

• According to the data from the randomized

controlled trials with long-term follow-up, the

reduction in mortality from women aged 40-49 is

49%! (Malmo II).

USPSTF Recommendations

• Used computer models to analyze data rather than using the

source data themselves

• Acknowledge that many of the trials show mortality benefit

for all women (including 40-49 y.o.) but then inexplicably

conclude that the “harms” (pain, anxiety, radiation dose,

false positives, unnecessary biopsies) outweigh the benefits

without showing any scientific analysis of the “harms”.

• None of the members of the task force have any experience

with mammographic screening or any aspect of imaging.

• 6,997 women diagnosed with breast cancer in

Massachusetts between 1990-99 (median f/u 12.5 yrs)

• ~ 80% of this population received regular screening

• 461 deaths from breast cancer:

– 345 (75%) of deaths occurred in women who did not

receive regular screening

– 116 (25%) of the deaths occurred in women who did

receive regular screening mammograms.

Cady B, et al (ASCO) 2009 Breast Cancer Symposium. Abstract 24

Screening Analysis: MA

Cady B, et al (ASCO) 2009 Breast Cancer Symposium.

• American Cancer Society: annual screening mammography

and CBE for all women beginning at age 40

• NCCN: annual screening mammography and CBE for

women 40 y.o and older at normal risk

• American College of Surgeons: annual screening

mammography beginning at age 40

• ACR: annual screening mammography beginning at age 40

• ASCO: “while the optimal scheduling of regular

mammograms is being discussed by experts in the field,

ASCO would not want to see any impediments to screening

mammography screening for any woman age 40 and above”

Screening Recommendations

Mammographic Assessment

What are we looking for ??

Mammographic Findings

• Mass

• Calcifications of Suspicious or

Indeterminate Appearance

• Architectural Distortion

• Mass

Possible Mass: Evaluation

Masses

• A mass is a space-occupying lesion which

is seen in two projections

• A potential mass which is seen only in a

single projection should be called an

asymmetry until its three-dimensionality

is confirmed.

• Focused Sonography

• Attempt to further characterize the

abnormality

• Simple cyst: return to annual

screening.

• Probable cyst with internal echoes:

aspirate for confirmation.

• Solid mass: core biopsy.

Possible Mass: Evaluation

SIMPLE CYST

LOBULATED MASS:

FIBROADENOMA

• Mass

Calcifications: Evaluation

• Diagnostic assessment of

mammographic calcifications

Distribution

Morphology

• Mass

Architectural Distortion: Evaluation

• Differential diagnostic considerations

Overlapping structures mimicking

abnormality

Area of prior surgery

Radial scar

Malignancy

• Sonographic findings cannot negate

mammographic findings

• Mammographic findings do not

supercede sonographic findings

• The management of any breast

abnormality is dictated by its most

worrisome features

Mammographic

Sonographic

Clinical examination

Percutaneous Biopsy:

Radiologic-Pathologic Correlation

In all breast biopsies, correlation of the

radiologic and pathologic findings is

critical to establish concordance

(agreement with the pre-procedure

expectation) or discordance

(disagreement with the pre-procedure

expectation).

If a percutaneous core biopsy yields a

benign diagnosis, it must explain the

imaging findings and correlate

favorably with the operator’s imaging

impression to be considered

concordant.

Core biopsy pathology results which are

discordant from the imaging findings

mandate additional tissue sampling.

• Re-biopsy

• Surgical excision

It is the responsibility of the individual

performing the biopsy to perform radiologic-

pathologic correlation on all percutaneous

biopsies; determine concordance or

discordance with the radiologic findings and

convey these impressions and

recommendations to the referring physician.

DIAGNOSIS: FIBROADENOMA----DISCORDANT

DIAGNOSIS: INVASIVE CARCINOMA-----CONCORDANT

DIAGNOSIS: FIBROCYSTIC CHANGE

WITH CALCIFICATIONS----DISCORDANT

DIAGNOSIS: DUCTAL CARCINOMA IN SITU

WITH CALCIFICATIONS----CONCORDANT

Women under 50 years of age

Women who were premenopausal or perimenopausal

Women classified as having heterogeneously dense or extremely dense breast tissue

Digital mammography performed significantly better in the detection of breast cancer.

Should different screening regimens be

implemented for women at high risk for

the development of breast cancer?

• Numbers of women at significantly increased levels of risk is small

• No randomized trials exist to assess impact of additional screening measures on mortality

• Recognition of genetic and pathologic identifiers of increased risk highlights the need for recommendations for suitable surveillance regimens in these subpopulations.

• Personal history of breast cancer

Annual mammography regardless of age

• Strong family history

Annual mammography beginning 10 yrs prior to age of first degree relative at diagnosis

• BRCA1 and BRCA2

Annual mammography beginning at age 25

• History of prior radiation in the late teens / early 20s

Annual mammography beginning 8 yrs after completion of radiation therapy

• BRCA1 and BRCA2

Annual mammography beginning at Age 25

• BRCA1 and BRCA2

Screening Strategies for BRCA Carriers

Lowry et al

• Used simulation models to compare screening strategies utilizing combinations of FSM, DM, and MRI in BRCA1 and 2 carriers

• Performed with and without estimation of attributable risk due to radiation exposure from mammography

• Found the most effective strategy was initiation of MRI screening at age 25 and then alternating DM and MRI at 6 month intervals beginning at age 30

• <4% of all diagnosed cancers were attributable to radiation exposure BRCA

Screening Strategies for BRCA Carriers

Lowry et al. Cancer 2012;118:2021-30.

Mammography is an imperfect tool…

20% of women diagnosed with cancer will have had a negative screening mammogram within the year prior to their diagnosis.

Breast Cancer Detection

• Mammography

• Ultrasound

• MRI

• Several single-center studies had shown the

ability to identify small non-palpable invasive

breast cancers which were occult on

mammography, particularly in dense breasts

• In these studies, the radiologist had not been

blinded to the mammographic results

Screening Breast Ultrasound

INVESTIGATOR YR NO. BX

Gordon et al. 199

5 12,706 2.2 16 100 0 0.35%

Buchberger et al. 200

0 8,103 4.1 8.8 88 13 0.39%

Kaplan 200

1 1,862 3.1 12 83 17 0.3%

Kolb et al. 200

2 13,547 2.6 10 97 3 0.27%

TOTAL 37,085 2.8 12.4 94.5 5.5 0.34%

CA HISTOLOGY

INV (%) DCIS (%)

Adapted from Berg. AJR: 180. May 2003

INVESTIGATOR YR NO. BX

Gordon et al. 199

5 12,706 2.2 16 100 0 0.35%

Buchberger et al. 200

0 8,103 4.1 8.8 88 13 0.39%

Kaplan 200

1 1,862 3.1 12 83 17 0.3%

Kolb et al. 200

2 13,547 2.6 10 97 3 0.27%

TOTAL 37,085 2.8 12.4 94.5 5.5 0.34%

CA HISTOLOGY

INV (%) DCIS (%)

Adapted from Berg. AJR: 180. May 2003

ACRIN Trial 6666

• Multicenter protocol

• High-risk asymptomatic women with dense breast

tissue

• 3 annual screening mammograms and sonograms

• Primary aim: to determine whether whole-breast

bilateral screening sonography can identify

mammographically occult cancers and whether such

results are generalizable across multiple centers.

ACRIN Trial 6666

• 2637 women at high risk for breast cancer

underwent screening mammography and ultrasound

• 41 cancers were found in 40 women (in total)

• 12 cancers were found by ultrasound alone

• The addition of ultrasound resulted in 136 (5.2%)

biopsies and the diagnosis of 14 cancers (yield of

ACRIN Trial 6666

• 2637 women at high risk for breast cancer

underwent screening mammography and ultrasound

• 41 cancers were found in 40 women (in total)

• 12 cancers were found by ultrasound alone

• The addition of ultrasound resulted in 136 (5.2%)

biopsies and the diagnosis of 14 cancers (yield of

• Mammography

• Ultrasound

• MRI

Can we build on the success of mammography?

Breast Cancer Detection

Breast Tomosynthesis

• Tomosynthesis is a 3-dimensional

mammographic technique.

• The technique essentially eliminates

“structured noise”.

Compression

paddle

• X-ray tube moves through

a prescribed arc of

excursion

• Multiple low-dose

projection images are

acquired during a 4-second

Detector

X-ray source

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

FFDM plus TOMO

Area (Az) - 2D plus 3D 0.90

Area (Az) - 2D 0.83

Difference 0.07

p value 0.0004

ALL CASES: POOLED 12 READERS

Rafferty et al. Radiology 2013; 266:104-113.

FFDM FFDM plus TOMO

Reader 2

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

Reader 3

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

Reader 4

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

Reader 5

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

Reader 6

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

Reader 7

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

Reader 8

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

Reader 9

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

Reader 10

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

Reader 11

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

Reader 12

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

ROC ANALYSIS BY READER

USING PROBABILITY OF MALIGNANCY SCALE

Reader 1

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

FFDM IMAGE

FFDM IMAGE TOMO IMAGE

Tomosynthesis: Dense Breasts

• For all cancer cases combined, the recall rate

for FFDM plus TOMO was 9.7% higher than

for FFDM alone

– 3.8% higher for calcification cases

‾ 14.3% higher for non-calcification

casescases

FFDM IMAGE

TOMO IMAGE FFDM IMAGE

Tomosynthesis: Recall Rate Analysis

Recall Analysis

• Every reader significantly reduced his / her

recall rate

• Recall rate reduction averaged 38.6%

*Based on assumption of 10% recall rate at baseline with FFDM alone

Recall Analysis

• Every reader significantly reduced his / her

recall rate

• Recall rate reduction averaged 38.6%

Rafferty et al. Radiology 2013; 266:104-113.

Tomosynthesis: Recall Rate Analysis

Future Directions:

Elimination of the conventional 2D mammogram

Achievement of biopsy capability on the 3D platform

Development of methodology to allow immobilization of the breast without full compression

Evaluation of contrast-enhanced techniques for tomosynthesis

Future Directions:

• Elimination of the conventional 2D mammogram

Achievement of biopsy capability on the 3D platform

• How does it work?

• Perform a standard

tomosynthesis scan

• How does it work?

tomosynthesis scan

• Reconstruct

tomosynthesis slices

15 Projection Images

Tomosynthesis Slices

Reconstruction

Algorithm

How does it work?

tomosynthesis scan

• Reconstruct

tomosynthesis slices

• Synthesize 2D image

(C-View)

C-View

Image Processing

Tomosynthesis Slices

Standard Mammogram

Standard Mammogram Synthetic Mammogram

Standard

Mammogram

Standard

Mammogram

Synthetic

Mammogram

Synthetic Mammogram: C-View

• C-View received its final approval for clinical use

by the FDA in May of 2013.

• Tomosynthesis in conjunction with C-View may be

used in any clinical situation in which a

mammogram is indicated.

Future Directions:

• Achievement of biopsy capability on the 3D platform

Future Directions:

• Development of methodology to allow immobilization of the breast without full compression

Future Directions:

• Development of methodology to allow immobilization of the breast without full compression

• Evaluation of contrast-enhanced techniques for tomosynthesis

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