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Estrogen, Androgen, Glucocorticoid, and Progesterone Receptors in Progestin-induced Regression of Human Breast Cancer¹

Departments of Biochemistry [F. T., M. S. H., H. P.] and Internal Medicine [H. van G., J. A-F.], Rotterdamsch Radio-Therapeutisch Instituut, Dr. Daniel den Hoed Kliniek, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands

A study was made of basic mechanisms involved in regression of breast cancer exposed to high levels of synthetic progestins. The possibility that progestins act on breast cancer by way of the progesterone receptor mechanism and subsequent increase of estradiol 17ß-dehydrogenase activity could not be confirmed in this investigation. It is demonstrated that 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. In contrast, these progestins do not compete with estradiol for estrogen receptor binding. In 34 patients with progressive metastatic breast cancer, results of receptor studies have been 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, while such correlations with estrogen and progesterone receptors were absent. However, we did demonstrate relationships between the quantities of the various receptors in breast cancer. Tumors containing a large amount of androgen receptors also generally contain estrogen receptors. It might be that a favorable response to progestins is confined to the group of patients with hormoneresponsive breast cancers, as such characterized by the presence of estrogen receptors, and that within this group the actual androgen receptor levels determine response.

¹ This work has been financially supported by the Dutch National Cancer League, the "Koningin Wilhelmina Fonds."

² To whom requests for reprints should be addressed.

Received 12/26/79. Accepted 4/ 8/80.

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