Sex steroids and breast cancer prevention

Mitogenesis and mutagenesis are major driving forces in neoplastic development. Little is known about important breast mutagens, but much is known about breast mitogens. "Blocking" the effect of breast cell mitogens, by reducing the actual exposure of the breast to them, is an obvious strategy for breast cancer prevention. The ovarian hormones, estrogens and progesterone, are major effective (direct or indirect) breast cell mitogens. There is overwhelming epidemiologic evidence that breast cancer risk is closely related to exposure to estrogens and progestogens. A woman's exposure to endogenous ovarian estrogens and progesterone is drastically reduced by the use of combination-type oral contraceptives (COCs), but the exogenous synthetic estrogen and progestogen in the COC effectively replace the ovarian estrogen and progesterone, so that no decrease in breast cell exposure to these hormones is obtained. Doses of estrogen and progestogen in modern COCs are close to the minimum attainable, while still retaining both contraceptive efficacy and ovarian suppression (so that endogenous estrogen and progesterone do not add to the dose of estrogen and progestogen from the COC). Considerably lower effective breast cell exposure to estrogen and progestogen can, however, be achieved by using a gonadotropin-releasing hormone agonist to suppress ovarian function and compensating for the resulting hypoestrogenemia with low-dose hormone replacement. Such a contraceptive is predicted to reduce lifetime breast cancer risk by more than 50% if used for 10 years and by as much as 70% following 15 years of use. Contraception represents a unique opportunity to have a substantial beneficial impact on women's health; more than 10 million women use COCs daily in the United States.(ABSTRACT TRUNCATED AT 250 WORDS)