Illustrative Case Series

Mammographic Breast Density and Breast Cancer Risk in Postmenopausal Women

By Jerome W. Yates, MD, Hematology/Immunology Unit, National Institute on Aging, NIH. Dr. Yates reports no financial relationships relevant to this field of study.

Case History

A 66-year-old postmenopausal retired teacher went to her primary care physician because she found a lump in her right breast during a routine bath. The primary care physician was unable to palpate a discrete mass in the area the patient identified and so the patient was referred for a mammogram. Her last mammography was 6 years ago and was normal. The current examination was normal with the exception of the finding that she has bilateral increased density without discrete abnormalities. When advised of the findings by the primary care physician, she said that she had read that dense breasts on mammograms increased the subsequent risk of developing breast cancer. She wanted to know whether she should do something different because of this increased risk.

Case Discussion

Breast density decreases as fat replaces glandular and connective tissue in postmenopausal women, while the incidence of breast cancer increases exponentially as women age until the age of about 85 years. A variety of case-control studies have shown that breast cancer risk is correlated with increased mammographic density.1 The increased risk appears to persist for 10 years or longer in spite of the progressive breast involution following menopause.2

A matched controlled study of breast cancer in postmenopausal nurses demonstrated an association between breast density and cancer risk.3 The association was stronger for cancer in situ than for invasive breast cancer, greater for undifferentiated than well-differentiated invasive cancer, greater for larger than smaller invasive cancers, and more associated with estrogen receptor negative than estrogen receptor positive tumors. Two explanations for the increased association with in situ cancer detection are suggested. The first is that women with dense breasts are more likely to undergo breast biopsies for suspicious lesions resulting in an oversampling and retrieval of a disproportionate number of in situ lesions. The second is that the correlation occurred by chance. The former explanation seems more plausible.

Statistical models for assessing breast cancer risk for younger women have received more attention than for their elderly counterparts. The combination of the "Gail Model" for risk assessment coupled with breast density measures failed to add better definition of breast cancer risk for women of all ages than the Gail model alone.4 An examination of relative contribution of breast density to the statistical constructs of Gail, Tice, Barlow, and Vermont were explored for women 70 years of age and older.5 These statistical models were not significantly enhanced by the addition of mammographic breast density in predicting a woman's risk of developing breast cancer.

Recommendations for breast cancer screening for elderly women should continue to be individualized based on their state of health and other influential components of the statistical models: age at menarche, history of postmenopausal estrogen replacement therapy, age when first child was born, history of previous breast biopsies, and body mass index (obesity). These epidemiologic contributions to the assessment of risk for an individual patient still require the guidance of solid clinical judgment from a knowledgeable physician. Mammographic breast density, although associated with the increased risk of breast cancer, contributes little to the modeled aggregation of other associations known to contribute or protect women from developing breast cancer.

References

1. Ginsburg OM, et al. Mammographic density, lobular involution, and risk of breast cancer. Br J Cancer 2008;99:1369-1374.

2. Byrne C. Studying mammographic density: Implications for understanding breast cancer. J Natl Cancer Inst 1997;89: 531-533.

3. Yaghjyan L, et al. Mammographic breast density and subsequent risk of breast cancer in postmenopausal women according to tumor characteristics. J Natl Cancer Inst 2011;103:1179-1189.

4. Tice JA, et al. Mammographic breast density and the Gail model for breast cancer risk prediction in a screening population. Breast Cancer Res Treat 2005;94:115-122.

5. Vacek PM, et al. Breast cancer risk assessment in women aged 70 and older. Breast Cancer Res Treat 2011;130:291-299.