Ovarian steroid hormones and anti-estrogens: Risks for and prevention of cancers of the breast and endometrium in the menopause

Most cellular and organ-specific effects of ovarian steroid hormones (e.g., estrogen and progesterone) are mediated by steroid-hormone receptors. However, the effects of these hormones can be lost despite the presence of receptors. Hormone replacement therapy reduces overall mortality but slightly increases the risk for breast cancer, regardless of the type of replacement therapy. Anti-estrogens such as tamoxifen and raloxifene, alone or in combination with steroid hormone replacement, reduce the incidence of breast cancer in women at low risk for the disease. Estrogen monotherapy and tamoxifen increase the incidence of endometrial cancer. Combined hormone replacement and raloxifene do not have this effect on the endometrium. Prospective studies of hormone replacement in patients with a history of breast or endometrial cancer are ongoing. The use of anti-estrogens for reducing the risk of breast cancer is being addressed in prospective trials with mortality as the primary endpoint. Currently hormone replacement in patients with a history of cancer of the breast or endometrium and anti-estrogens for prevention of breast cancer should be limited to clinical trials.