Endocrine alterations such as hypophysectomy, adrenalectomy and oophorectomy, as well as administration of pharmacological doses of estrogens, progestins, androgens and corticosteroids, have been shown to induce significant temporary regression of metastatic breast cancer in some women. Studies of the mechanism by which such endocrine alterations induce tumor regression, suggest that prolactin and estrogens are the most important hormones involved in maintaining the growth of hormone-dependent mammary cancers in women and in rats. Specific receptor sites for prolactin and estrogen have been demonstrated in some mammary cancers from women and rats, and these measurements appear to provide useful markers of the hormone dependence of the cancers. A prolactin inhibitor drug and an antiestrogen drug are under study for their anti-tumor effects in rats and women. A major goal is to develop a "medical hypophysectomy" for the therapy of women with breast cancer. Optimal endocrine therapy will be combined with optimal cytotoxic chemotherapy in patients with advanced disease to determine whether this will be more effective than sequential therapies. A prospective, randomized study of adjuvant endocrine therapy, cytotoxic chemotherapy and immunotherapy for patients with Stage II primary breast cancer has been designed to determine whether early systemic treatment when the tumor burden is low, may produce cures or prolonged survival free of detectable disease. BIBLIOGRAPHIC REFERENCES: Estrogen Binding Protein of Rat Liver. P. Viladiu, C. Delgado, J. Pensky and O. H. Pearson. Endoc. Res. Commun. 2(3), 273-280 (1975). Estrogen Receptors and Prediction of the Response of Metastatic Breast Cancer to Hypophysectomy. O.H. Pearson, W.L. McGuire, J. Brodkey and J. Marshall. Chapter Four in "Estrogen Receptors in Human Breast Cancer" Ed. W. L. McGuire, E. P. Voolmer and P. P. Carbone, Raven Press, New York, 1975.