Assessing and Managing the Risk of Breast Cancer in Postmenopausal Women: Opportunities and Challenges

A number of factors are known to increase the risk of developing breast cancer. The most important of these is age, but race and ethnicity are associated with important differences in risk. Nulliparity and birth events, benign breast disease, and the use of replacement hormonal therapy at menopause also contribute to risk. Family history and the presence of predisposing genetic mutations are important factors as is ethanol consumption. Circulating estrogen levels can stratify risk, but their use in clinical settings is not routine. Risk for breast cancer can be easily and rapidly assessed in the clinic, and validated, quantitative models are available to accomplish this task. Mammographic breast density identifies postmenopausal women who are at increased risk. Multiple, published, randomized studies show that the selective estrogen response modifiers (SERMs) tamoxifen and raloxifene can safely reduce the risk of invasive breast cancer in both preand postmenopausal women. Tamoxifen provides net benefit to all premenopausal women who are at increased risk while raloxifene reduces risk nearly as much in postmenopausal women and offers increased safety. Both tamoxifen and raloxifene reduce both the incidence of in situ cancers and bone fractures. Women with a history of benign breast disease and a family history of invasive breast cancer in first-degree relatives and women with lobular carcinoma in situ derive substantial net benefit when using SERMs for breast cancer risk reduction. Of the 50 million white women in the U.S. aged 35 to 79 years, 2.4 million would have a positive benefit/risk index for chemoprevention.

Keywords: Quantitative Risk Assessment; Risk Reduction; Primary Prevention; Selective Estrogen Response Modifiers; Tamoxifen, Raloxifene.