Menopausal Estrogen Therapy and Risk of Breast Cancer

Recent evidence suggests that use of menopausal estrogen-only therapy in patients who have undergone hysterectomy reduces breast cancer risk among patients at population risk for breast cancer as well as in those with pathogenic high-risk BRCA variants. A meta-analysis of 10 randomized trials of estrogen therapy compared with placebo among 14,282 participants at population risk noted that 3.6% those randomized to estrogen alone were diagnosed with breast cancer, compared with 4.7% of those randomized to placebo (relative risk 0.77; 95% CI, 0.65-0.91, P=.002). A matched prospective cohort study of 676 patients with BRCA mutations and intact breasts who used menopausal hormone therapy (MHT) found that the estimated 15-year cumulative incidence of breast cancer with estrogen alone compared with no MHT was 24.3%, compared with 47.3% in the matched nonusers of MHT (P<.0001). This evidence underscores the need for more data that specifically assess the effect of estradiol therapy among patients who have undergone hysterectomy. Until such data are available, counseling patients at risk for breast cancer who have completed childbearing and are planning surgery for benign gynecologic conditions should involve shared decision-making that addresses the future risk of breast and endometrial cancers, cardiovascular disease, as well as the morbidity associated with hysterectomy. When appropriate, such counseling should also describe the availability of uterine-sparing alternatives.