Mills-Peninsula Health Services 2013 Cancer Symposium, Harriet B. Borofsky, M.D. Medical Director of Breast Imaging Mills-Peninsula Women’s Center

1. “Dense Breasts”: The Facts, The
Myths, The Law
Harriet B. Borofsky, M.D.
Medical Director of Breast Imaging
Mills-Peninsula Women’s Center

2. Outline
• Background: Why and how we screen for breast cancer
• The “Dense Breast” Law: Senate Bill 1538
• “Dense Breasts” : The Facts and The Myths
– Mammographic breast patterns
– Limitations of mammography in women with “dense”
breasts
– Breast density and age
– Breast density as an independent risk factor for breast
cancer
• Implications of the law: Supplemental screening;
ultrasound, MRI and Digital Breast Tomosynthesis
(DBT).

3. Breast Anatomy

4. Breast Cancer
• Most frequently diagnosed, non skin, cancer
in women
• Statistics: (ACS most recent estimates)
– 226,870 new diagnosis/year in U.S.
• 4,500 cases/year; 12 cases/day in Bay Area
– 63,000 new diagnosis of DCIS/year in U.S.
– 39, 510 deaths due to breast cancer/year in U.S.
• 1,000 deaths/year in Bay Area

5. Breast Cancer Types
• Heterogeneous disease: different types and
subtypes based on cell of origin, in situ or
invasive and phenotypic expression
• Invasive 75%
– Ductal 90%
– Lobular 10%
• Ductal carcinoma in-situ (DCIS) 25%

6. Breast Cancer Subtypes: based on
tumor specific gene expression
• Endorsed by St. Gallen International Expert Consensus
Panel; 2011
• Determined by Immunohistochemistry (IHC)
• Expression of estrogen and progesterone receptors,
HER2 oncogene and Ki-67 antigen
• Allows for targeted, individualized approaches:
hormonal therapy, endocrine therapy, Herceptin
• Four subtypes-
– Luminal A: ER+, HER2-, Ki-67 low
– Luminal B: ER+, HER2- and Ki-67 high or HER2+
– HER2+: ER-, HER2+
– Basal like: Triple negative; ER-, PR- HER2-

7. Who is at risk for breast cancer?
• Women – Overall lifetime risk of 14%; 1 in 7,
based on life expectancy of 85 years
• Advancing Age

8. Who is High-Risk for Breast Cancer?
• Personal history of breast cancer
• First degree relative/s with breast cancer
• Inherited genetic mutations; BRCA1 and
BRCA2: Hereditary Breast and Ovarian Cancer
Syndrome
• Exposure to radiation at young age
• Prior biopsy showing atypia: atypical ductal
hyperplasia and/or lobular neoplasia

9. Risk Associations
• Early menarche
• Late menopause
• Nulliparity
• Hormonal therapy: estrogen and progesterone
• Post menopausal obesity
• Alcohol consumption
• Breast Density

10. Why Screen for Breast Cancer?
• Most common malignancy in women
• Second leading cause of cancer death in
women
• It is a progressive disease: Early detection
offers opportunity to halt natural evolution,
increase treatment options; and ultimately,
save lives.

11. Screening Test: Mammography
• Relatively inexpensive
• Safe and well tolerated
• Readily accessible to large population of
women
• Sensitive and specific
• Proven to be efficacious in reducing mortality
from breast cancer

12. Proof of Benefit – Randomized Controlled
Trials (RCTs)
• HIP – Health Insurance Plan of New York (1963); ages
40-64; 23% mortality reduction
• 2-County Swedish Trial (1977); ages 40-74; 34%
mortality reduction
• Gothenburg (1982): ages 39-59; 44% mortality
reduction
• Malmo (1976): ages 45-69; 36% mortality reduction
• Meta-analysis (Hendricks et al) women in 40’s: 29%
mortality reduction

13. Proof of Benefit
• Since population-based screening initiated in
1990s, death rate from breast cancer has
decreased by 2.2%/year
• The estimated mortality reduction from breast
cancer due to screening is 28-65%

14. Early Detection has led to Paradigm
Shift in Management of Breast Cancer
• Increasing number of early stage, node
negative breast cancers:
– Less invasive surgical procedures: Sentinel
lymph node biopsy
– Partial breast radiation (APBI)
– Gene expression profiling technologies
(Oncotype Dx, Mammoprint ) to determine
which early stage, lymph node negative
patients may forego chemotherapy

15. Mills-Peninsula Breast Program
Breast Cancer Data 2011
• Total Women screened: 21,274
• Women called back: 3,254 (15.3%)
• Breast Cancers Detected (Yield): 145
• Cancer Detection rate: 7.2/1000 (4.2/1000 Nat'l avg)
MP Breast Program Nat’l Data
DCIS (Stage 0) 43% 24%
Minimal 66% 53%
Stage 0 and 1 83% 73%
Lymph node + 7% 24%
Sensitivity 93% 88%

16. American Cancer Society (ACS)
Screening Guidelines
• Baseline mammogram by age 40
• Annual mammogram, age 40 and above.
• For women with first degree relative with
premenopausal breast cancer, begin screening
10 years earlier than age at relative’s diagnosis
(but above age 30).

17. Limitations/Risks of Screening
Mammography
• Costly: Contributes significantly to overall
national health care costs
• False positives: additional views (call backs),
biopsies, inconvenience and anxiety.
• Theoretical over diagnosis: Some cancers
detected and treated might never have caused
death
• Radiation exposure
• False negatives: missed breast cancer; false sense
of security and potential delay in treatment

18. “Dense Breast” Senate Bill 1538,
Chapter 458
• Authored by Senator Joe Simitian (D-Palo Alto)
• Modeled after “dense breast” legislation that
first passed into law: Connecticut Public Act
09-41
• Other states with similar laws: Utah, Virginia,
New York, and Texas
• Signed by Governor Jerry Brown, September,
2012; takes effect April 1, 2013

19. SB 1538: Comprehensive
Breast Tissue Screening
(2012)
THE PEOPLE OF THE STATE OF CALIFORNIA DO ENACT AS
FOLLOWS:

20. SB 1538
• Existing law (MQSA 1998) requires that
patients receive a written summary of their
mammogram results.
• New law requires that women, in the state of
California, also receive, in their summary
report, a prescribed notice if their breasts are
dense, based in ACR’s BIRADS breast pattern
types 3 or 4:

21. Breast Density Notice
• “Your mammogram shows that your breast tissue is
dense. Dense breast tissue is common and is not
abnormal. However, dense breast tissue can make it
harder to evaluate the results of your mammogram
and may also be associated with an increased risk of
breast cancer.”
• This information about the results of your
mammograms is given to you to raise your awareness
and to inform your conversations with your doctor.
Together, you can decide which screening options are
right for you. A report of your results was sent to your
physician.

22. ACR’s BIRADS (Breast Imaging Reporting
and Data System) : Breast Patterns Types
• Type 1: Fatty – almost entirely fatty tissue
• Type 2: Average- 25%-50% fibroglandular
tissue
• Type 3: Heterogeneously Dense- 50%-75%
fibroglandular tissue
• Type 4: Extremely Dense- >75% fibroglandular
tissue

23. Type 1: Fatty replaced Type 2: Average
Type 3: Heterogeneously Type 4: Very dense
Dense

24. Breast Density- Facts
• Marked heterogeneity in the mammographic
appearance of women’s breasts
• “Dense” breast patterns are common: 40% of
mammograms are types 3 and 4
• Breast density is genetic and altered some by
advancing age and hormonal influences
• Mammographic sensitivity is inversely related to
breast density
• Mammogram still invaluable in assessing for
interval changes, architectural distortion, and
calcifications and should be performed

25. Mandelson et al. J Natl Cancer Inst 2000;
931: 1081-1087)
• Mammographic sensitivity of 80% in women
with fatty breasts
• Mammographic sensitivity of 30% in women
with extremely dense breasts
• Odds ratio for interval cancers among women
with extremely dense breasts: 6.14, compared
to women with fatty breasts.

26. Breast Density and Sensitivity of
Mammography
Mills-Peninsula Breast Program: 2004-
2008
Breast Density Percentage of patients Overall Sensitivity
Fatty 5.9% 93%
Average 56.9% 88%
Heterogeneously Dense 33.7% 84%
Extremely Dense 3.5% 71%

27. Developing Density: IDC
Developing Density: IDC Asymmetry: ILC
Clustered calcification: Nodule: IDC
DCIS

28. Breast Density and Age: Myth
• Pre-menopausal women have dense breasts
and mammograms are not sensitive or useful
• Post-menopausal women have fatty breasts
and they alone benefit from mammography

29. Breast Density and Age
• Checka et al. Density and Age: Implications for
Breast Cancer Screening. AJR; March, 2012.
• Retrospective review of 7007 mammograms
at New York University Langone Medical
Center; 2008.
AGE RANGE % with DENSE BREASTS
40-49 74%
50-59 57%
60-69 44%
70-79 36%

30. Breast Density and Age
• Genetics may play larger role in breast density
than age and menopausal status.
• Breast density may be altered by hormonal
changes:
– Pregnancy/lactation
– Hormonal therapy; especially estrogen/progesterone
– Tamoxifen
• Mortality reduction from breast cancer in women
screened, has been achieved in all age categories;
40 through 74.

31. Are Women with “Dense Breasts” at
Increased Risk for Breast Cancer?
• Breast density is increasingly recognized as a
independent risk factor for developing breast
cancer.
• Multiple retrospective studies show the odds
ratio for developing breast cancer in the least
dense compared to the most dense breast issue
ranges from 1.9-6.0, with most studies yielding an
odds ratio of 4.0 or greater. Harvey et al.
Radiology. 2004.
• Validity of studies debated due to subjectivity in
assigning breast density; based on 2D imaging.

32. Ongoing Questions?
• What is the mechanism by which density may
affect breast cancer risk?
• What component/s of dense breasts,
epithelial vs stromal, imparts risk?
• Does reduction in breast density lead to lower
risk?
• Are mammograms enough?

33. Supplemental Imaging Modalities
• Breast ultrasound
• MRI
• Digital Breast Tomosynthesis (DBT)

34. Breast Ultrasound

35. Breast Ultrasound for Screening
• Invaluable adjunct to mammography
• Advances in high frequency, 14 MHz transducers has
led to improved resolution and increased utilization
• Easy to perform and well tolerated
• Safe: No radiation
• Cross-sectional imaging; no overlapping tissue
• Not impeded by breast density

36. Literature: Screening Breast
Ultrasound
• In high-risk women with dense breasts:
– Kolb et al. Radiology 2002: Increased breast cancer
rate by 13%
– ACRIN 6666; JAMA, 2008: Increased breast cancer
detection rate by 28%
• Three multi-center trials: ultrasound increased
breast cancer detection (yield) by 4.2-4.4/1000
• Six single-center studies: ultrasound increased
breast cancer detection (yield) by: 3.5/1000
• Majority: node-negative, early stage invasive
cancers

37. Hooley et al. Screening US in patients with Mammographically
Dense Breasts: Initial Experience with Connecticut Public Act 09-
41. Radiology; 2012; 265: 59-69.
• Yale, New Haven, data from first year of
implementation of law
• 935 women with dense breast tissue and
normal mammograms received supplemental
US screening
• 5% (47) suspicious ultrasound finding
requiring biopsy
• PPV for biopsy was 6.5%
• Overall cancer detection rate: 3.2/1000

38. Weigert, et al. The Connecticut Experiment: The Role of
Ultraound in the Screening of Women with Dense
Breasts. The Breast Journal. 2013. 18: 517-522
• 12 sites in Connecticut; Norwalk and New Britain
• Retrospective study
• 72,030 screenings; 28,812 dense with normal
mammograms
• 30%; 8,647 elected to have recommended US
• 5% suspicious US finding
• PPV 6.7%
• 3.25 additional cancers/1000 women

39. Screening Breast Ultrasound: Mills-
Peninsula 2011 Data
• Performed 1,432 screening breast ultrasound
in women with dense breasts
• 7 ultrasound-detected cancers.
• Additional 4.9 cancers/1,000 women
• Increase in breast cancer detection rate: 5%

40. Breast Ultrasound: Limitations
• Resources: staff and time intensive; low
reimbursement
• Operator/experience and equipment dependent
• ACR accreditation not required; variable quality
of care
• No mandate for insurance coverage
• False positive rate; low PPV
– ACRIN 6666; JAMA, 2008: Adding US to
mammography results in 4x as many false positives.

42. Breast MRI

43. American Cancer Society: Breast MRI
Screening Guidelines: 2007
• Annual breast MRI screening, in addition to
mammography, in the following high risk
women:
– Known BRCA1/BRCA2 mutations
– First degree relative of known mutations
– Greater than 20% lifetime risk based on computer
risk assessment models
– Chest radiation therapy between ages 10-30
– Li-Fraumeni, Cowden and Bannayan-Riley-
Ruvalcaba syndromes and first degree relatives

45. Breast Cancer Detection Yield of MRI
• Nine studies evaluating role of MRI in addition
to mammography in high risk women:
• Increase in breast cancer detection (yield) of
11-14/1000
• No studies evaluating efficacy of MRI
specifically in women with dense breasts.

46. Breast MRI: Limitations
• Costly; No mandate for insurance coverage
• Difficult exam: Requires intravenous contrast,
time intensive, uncomfortable
• Lacks specificity
• Competition for scanner time

47. Digital Breast Tomosynthesis (DBT)
• Advanced application of digital mammography.
• In early phases of clinical evaluation
• FDA approved for Hologic’s Selenia 3D
Dimensions System, February, 2011
• Utilizes multiple, limited-angle tomographic
images through a compressed breast during a 4
second exposure
• Images are reconstructed at 1 mm thin sections
and displayed on high resolution monitors along
with standard views

48. DBT
• Improves upon the major limitation of
mammography: overlapping tissue leading to
missed cancers and additional evaluation for
normal exams
• May increase lesion conspicuity, thus increase
breast cancer detection rate
• Early European studies: reduces call back rate by
40%
• No studies assessing efficacy specifically in
women with dense breasts

49. The 2D Mammography Image next to one slice of a DBT Image Set
2D DBT
The Difference is Clear
Hologic – Proprietary and Confidential

50. Summary
• New law requires that patients be notified if they have
“dense breasts” and informed that:
– The sensitivity of mammography is decreased in women
with dense breasts
– Breast density may be associated with an increased risk for
breast cancer
• Referring doctors will be informed of breast density in
patient’s official mammography report
• Ultrasound may be most effective supplemental
approach in improving early breast cancer detection in
women with dense breasts; especially those at
intermediate risk who do not meet risk criteria for MRI

51. Summary
• MRI has important role in smaller subset of
high-risk women with dense breasts who
meet ACS criteria
• DBT will improve breast cancer detection and
will eventually become standard of care in
mammographic screening
• Screening options will become increasing
tailored for the individual woman, based on
age, breast density and other risk factors.