Breast cancer prevention through modulation of endogenous hormones.

The use of exogenous sex-steroids for hormonal contraception is important to the way of life of many modern women. The widespread use of hormonal contraceptives represents a unique opportunity to have a substantial positive impact on women's health. The observation that users of oral combination type contraceptives have a reduced risk of ovarian cancer should encourage the extension of contraceptive development to address the most important malignancy facing modern women, breast cancer. Epidemiological evidence strongly suggests that both estrogens and progestogens contribute to breast cancer risk, and account for the steep rise in risk seen during the premenopausal years. Studies of normal breast epithelial cell proliferation confirm that progestogens are breast mitogens, and explain why current contraceptives, which are progestogen dominant, do not prevent breast cancer. A long-acting depot contraceptive can be developed which releases: 1) an agonist of gonadotropin releasing hormone to suppress ovarian function; and 2) sex-steroids at doses below those in current contraceptives, and below those associated with ovulation. Such a contraceptive should provide substantial life-time protection against both breast and ovarian cancer, and would retain many of the other health benefits of current contraceptives.