William L. McGuire Memorial Symposium. Estrogen and progestin effects in human breast carcinogenesis

The influences of estrogen and progestin on human mammary neoplasia are reviewed with a view to identifying what is known about their effects. Estrogens promote growth of established cancer and pharmacological levels of progestins induce remission. In vivo, highest proliferation of histologically normal mammary epithelium occurs in the progestogenic phase of the menstrual cycle or under the progestogenic influence of oral contraceptives. Little additional hard data exist to indicate whether progestins promote or inhibit human mammary carcinogenesis. Effects on proliferation, steroid receptor content and development are discussed together with interpretation of epidemiological data on risk factors that have hormonal components. Progestins may not be the benign or beneficial agents previously supposed, and there are virtually no data to suggest that they are antiestrogenic. It is hypothesized that carcinogenesis may be accompanied by increased sensitivity to estrogen, which provides a growth advantage to the tumor by maximizing use of the low estrogen concentrations encountered in the postmenopausal state.