“Dense Breasts”: The Facts, The Myths, The Law

Harriet B. Borofsky, M.D.Medical Director of Breast Imaging

Mills-Peninsula Women’s Center

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).

Breast Anatomy

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

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%

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-

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

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

Risk Associations

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

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.

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

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

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%

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

Mills-Peninsula Breast ProgramBreast 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%

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).

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

“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

SB 1538: Comprehensive Breast Tissue Screening

(2012)

THE PEOPLE OF THE STATE OF CALIFORNIA DO ENACT AS FOLLOWS:

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:

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.

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

Type 1: Fatty replaced Type 2: Average

Type 3: Heterogeneously Dense

Type 4: Very dense

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

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.

Breast Density and Sensitivity of Mammography

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%

Mills-Peninsula Breast Program: 2004-2008

Developing Density: IDC Asymmetry: ILC

Clustered calcification: DCIS

Nodule: IDC

Developing Density: IDC

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

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%

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.

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.

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?

Supplemental Imaging Modalities

• Breast ultrasound• MRI• Digital Breast Tomosynthesis (DBT)

Breast Ultrasound

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

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

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

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

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%

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.

Breast MRI

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

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.

Breast MRI: Limitations

• Costly; No mandate for insurance coverage• Difficult exam: Requires intravenous contrast,

time intensive, uncomfortable• Lacks specificity • Competition for scanner time

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

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

2D DBT

Hologic – Proprietary and Confidential

The 2D Mammography Image next to one slice of a DBT Image Set

The Difference is Clear

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

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.