ESTROGEN, ANDROGEN, GLUCOCORTICOID, AND PROGESTERONE RECEPTORS IN PROGESTIN-INDUCED REGRESSION OF HUMAN-BREAST CANCER

Abstract

Basic mechanisms involved in regression of breast cancer exposed to high levels of synthetic progestins were studied. The possibility that progestins act on breast cancer by way of the progesterone receptor mechanism and subsequent increase of estradiol 17.beta.-dehydrogenase activity could not be confirmed. The progestins megestrol acetate and medroxyprogesterone acetate are strong competitors for steroids which bind specifically to androgen, glucocorticoid and progesterone receptors, indicating that the progestins are able to bind to these receptors with high affinity. These progestins do not compete with estradiol for estrogen receptor binding. In 34 patients with progressive metastatic breast cancer, results of receptor studies were correlated with clinical response during treatment with megestrol acetate. Statistically, regressions were significantly associated with tumors containing large amounts of androgen receptors. Clinical correlation with the quantities of glucocorticoid receptor was weak; such correlations with estrogen and progesterone receptors were absent. Relationships between the quantities of the various receptors in breast cancer were demonstrated. Tumors containing a large amount of androgen receptors generally contain estrogen receptors. A favorable response to progestins may be confined to the group of patients with hormone-responsive breast cancers, as such characterized by the presence of estrogen receptors; within this group the actual androgen receptor levels probably determine response.