Epidemiology, genetics, and risk evaluation of postmenopausal women at risk of breast cancer.

Breast cancer risk factors have been studied for the past three decades, and the single most important risk factor is age. Hormonally linked adult reproductive and anthropometric risk factors contribute to the etiology of postmenopausal breast cancer. The risk of breast cancer increases among women older than 50 years of age who have benign breast disease, especially those with atypical ductal or lobular hyperplasia. Lobular carcinoma in situ increases risk significantly, as do a family history of breast cancer in first-degree relatives and the presence of BRCA1 or BRCA2 mutations. Diet, exercise, and environmental factors play a very small role in overall risk. Mammographic breast density increases relative risk fivefold among women with the highest density, and breast cancer risk is two to three times greater in women with elevated serum levels of estradiol or testosterone. Multivariate risk models allow determination of composite relative risks and cumulative lifetime risk, although improved models for African American women are required. For postmenopausal women, newer risk models are being developed and validated that include age, breast density, race, ethnicity, family history of breast cancer, a previous breast biopsy, body mass index, age at onset of natural menopause, hormone therapy, and previous false-positive mammography. A simpler model that includes only age, breast cancer in first-degree relatives, and previous breast biopsy performs well for estrogen receptor-positive breast cancer in postmenopausal women. As many as 10 million women in the United States are at increased risk, and clinicians are obligated to identify these women and manage their risk appropriately.