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 17 beta-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
hormone-responsive breast
cancers, as such characterized by the presence of
estrogen receptors, and that within this group the actual
androgen receptor levels determine response.