EARLY DETECTION: MAMMOGRAPHY AND SONOGRAPHY

EARLY DETECTION: MAMMOGRAPHY AND 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.

Breast Cancer Screening Screening for breast cancer Mammography Ultrasound MRI

Breast Cancer Screening 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 y.o. 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

Breast Cancer Screening 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.

Screening Analysis: MA 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. Abstrac Cady B, et al (ASCO) 2009 Breast Cancer Symposium.

Screening Recommendations 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

Mammographic Assessment What are we looking for??

Mammographic Findings Mass Calcifications of Suspicious or Indeterminate Appearance Architectural Distortion

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.

Possible Mass: Evaluation 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.

LOBULATED MASS: FIBROADENOMA SIMPLE CYST

Mammographic Findings Mass Calcifications of Suspicious or Indeterminate Appearance Architectural Distortion

Calcifications: Evaluation Diagnostic assessment of mammographic calcifications Distribution Morphology

Mammographic Findings Mass Calcifications of Suspicious or Indeterminate Appearance Architectural Distortion

Architectural Distortion: Evaluation Differential diagnostic considerations Overlapping structures mimicking abnormality Area of prior surgery Radial scar Malignancy

Mammographic Assessment Sonographic findings cannot negate mammographic findings Mammographic findings do not supercede sonographic findings

Mammographic Assessment The management of any breast abnormality is dictated by its most worrisome features Mammographic Sonographic MRI 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).

Percutaneous Biopsy: Radiologic-Pathologic Correlation 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.

Percutaneous Biopsy: Radiologic-Pathologic Correlation Core biopsy pathology results which are discordant from the imaging findings mandate additional tissue sampling. Re-biopsy Surgical excision

Percutaneous Biopsy: Radiologic-Pathologic Correlation It is the responsibility of the individual performing the biopsy to perform radiologicpathologic 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

DMIST In: 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.

Breast Cancer Screening Should different screening regimens be implemented for women at high risk for the development of breast cancer?

Breast Cancer Screening 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.

Breast Cancer Screening 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

Breast Cancer Screening 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

Screening Strategies for BRCA Carriers BRCA

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

Breast Cancer Detection 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 Screening Screening for breast cancer Mammography Ultrasound MRI

Screening Breast Ultrasound 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

INVESTIGATOR YR NO. BX BX Gordon et al. 199 5 (%) PPV BX (%) CA HISTOLOGY INV (%) DCIS (%) PREV BX (%) 12,706 2.2 16 100 0 0.35% Buchberger et al. 200 0 Kaplan 200 1 Kolb et al. 200 2 8,103 4.1 8.8 88 13 0.39% 1,862 3.1 12 83 17 0.3% 13,547 2.6 10 97 3 0.27% TOTAL 37,085 2.8 12.4 94.5 5.5 0.34% Adapted from Berg. AJR: 180. May 2003

Screening Breast Ultrasound 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.

Screening Breast Ultrasound 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 8.5%)

Breast Cancer Screening Screening for breast cancer Mammography Ultrasound MRI

Breast Cancer Detection Can we build on the success of mammography?

Breast Tomosynthesis Tomosynthesis is a 3-dimensional mammographic technique. The technique essentially eliminates structured noise.

Breast Tomosynthesis X-ray source X-ray tube moves through a prescribed arc of excursion Compression paddle Multiple low-dose projection images are acquired during a 4-second sweep Detector

RMLO 2D

2D 3D

TPF ALL CASES: POOLED 12 READERS 1 0.9 FFDM plus TOMO 0.8 0.7 0.6 FFDM 0.5 0.4 0.3 0.2 0.1 0 Area (Az) - 2D plus 3D 0.90 Area (Az) - 2D 0.83 Difference 0.07 p value 0.0004 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 FPF Rafferty et al. Radiology 2013; 266:104-113.

TPF TPF TPF TPF TPF TPF TPF TPF TPF TPF TPF TPF ROC ANALYSIS BY READER USING PROBABILITY OF MALIGNANCY SCALE 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 Reader 1 2D 2D &D 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 FPF 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 Reader 2 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 FPF 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 Reader 3 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 FPF 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 Reader 4 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 FPF 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 Reader 5 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 FPF 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 Reader 6 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 FPF 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 Reader 7 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 FPF 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 Reader 8 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 FPF 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 Reader 9 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 FPF 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 Reader 10 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 FPF 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 Reader 11 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 FPF 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 Reader 12 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 FPF FFDM FFDM plus TOMO

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

FFDM IMAGE TOMO 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

Tomosynthesis: Recall Rate Analysis Recall Analysis Every reader significantly reduced his / her recall rate Recall rate reduction averaged 38.6% Rafferty et al. Radiology 2013; 266:104-113.

Breast Tomosynthesis 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

How does it work? Perform a standard tomosynthesis scan

Tomosynthesis Slices How does it work? Perform a standard tomosynthesis scan Reconstruct tomosynthesis slices Reconstruction Algorithm 15 Projection Images

Tomosynthesis Slices How does it work? Perform a standard tomosynthesis scan Reconstruct tomosynthesis slices Image Processing Synthesize 2D image (C-View) C-View

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.