Hormones and breast cancer

The role of estrogen replacement therapy in the cause of breast cancer continues to be debated. This article reviews the literature on hormones and breast cancer, including articles on cell proliferation, endogenous hormone levels, epidemiologic studies, and the risk of breast cancer. A cause of cancer is defined as a factor that increases the probability that cancer will develop in an individual. A causal relationship between female hormones and breast cancer is consistently suggested by several lines of argument, especially the relationship between duration of use and risk of breast cancer, dose-response with endogenous hormone levels, and biologic plausibility. The magnitude of the increase in risk of breast cancer caused by using hormone replacement is comparable to that seen in delayed menopause. The positive correlation between endogenous hormone levels and risk of breast cancer supports a causal relationship between exogenous hormone use and breast cancer. The increase in risk of breast cancer with increasing duration of use, which does not vary substantially across studies, offers further evidence for a causal relationship. The reduction in mortality rate with short-term use of hormones, although strongest among women with risk factors for cardiovascular disease, adds complexity to the risk-to-benefit trade-off associated with long-term hormone use. All evidence supports a causal relationship between both endogenous estrogens and the use of estrogens and progestins, and breast cancer incidence in postmenopausal women. Hormones act to promote the late stages of carcinogenesis among postmenopausal women and to facilitate proliferation of malignant cells. Strategies for relief of menopausal symptoms and long-term prevention of osteoporosis and heart disease that do not cause breast cancer are urgently needed.