EARLY DETECTION: MAMMOGRAPHY AND SONOGRAPHY Elizabeth A. Rafferty, M.D. Avon Comprehensive Breast Center Massachusetts General Hospital Harvard Medical School
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
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
• 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).
Breast Cancer Screening
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
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.
• 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
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).
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 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.
Percutaneous Biopsy:
Radiologic-Pathologic Correlation
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.
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.
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.
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?
• 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
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
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
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
Breast Cancer Screening
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
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
Breast Cancer Screening
Screening for breast cancer
• 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
BX
(%)
PPV
BX
(%)
PREV
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
BX
(%)
PPV
BX
(%)
PREV
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.
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%)
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%)
Screening Breast Ultrasound
Breast Cancer Screening
Screening for breast cancer
• 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
sweep
Detector
X-ray source
Breast Tomosynthesis
RMLO
2D
RMLO
2D
2D 3D
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
FPF
TP
F
FFDM plus TOMO
Area (Az) - 2D plus 3D 0.90
Area (Az) - 2D 0.83
Difference 0.07
p value 0.0004
FFDM
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
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
FPF
TP
F
Reader 3
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
FPF
TP
F
Reader 4
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
FPF
TP
F
Reader 5
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
FPF
TP
F
Reader 6
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
FPF
TP
F
Reader 7
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
FPF
TP
F
Reader 8
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
FPF
TP
F
Reader 9
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
FPF
TP
F
Reader 10
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
FPF
TP
F
Reader 11
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
FPF
TP
F
Reader 12
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
FPF
TP
F
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
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
FPF
TP
F
2D
2D &D
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
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
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
Breast Tomosynthesis
• How does it work?
• Perform a standard
tomosynthesis scan
• How does it work?
• Perform a standard
tomosynthesis scan
• Reconstruct
tomosynthesis slices
15 Projection Images
Tomosynthesis Slices
Reconstruction
Algorithm
How does it work?
• Perform a standard
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:
• 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
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
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
Breast Tomosynthesis