Hormonal and cytotoxic chemotherapy for endometrial carcinoma. Steroid receptors in the selection of appropriate therapy.

Abstract

Progestin therapy yields an objective remission in about one‐third of patients with advanced endometrial carcinoma. Cytotoxic chemotherapy has also clearly proved effective in recent years, and anti‐estrogen therapy to an indicative degree. It is remarkable that both these therapies appear to exert their anti‐neoplastic effect even in patients unresponsive to progestin.A survey of current knowledge on estrogen (ER) and progestin receptors (PR) demonstrates that they are present simultaneously in 41 ‐ 80% of samples of endometrial carcinoma tissue. The concentration of cytosol ER and PR tends to decrease from well differentiated towards anaplastic carcinomas. This indirect evidence, together with some preliminary clinical observations, suggests that an absence or low concentration of ER and/or PR is suggestive of a poor prognosis.It is thought that an assay of ER and PR might be of value in predicting the response to chemotherapy in endometrial carcinoma, such as in breast carcinoma. This does indeed seem to be the case, as at least four independent clinical studies have to date confirmed that significant amounts of cytosol ER alone, and especially cytosol PR alone, or both together, in the tumor tissue can predict with reasonable accuracy a good sensitivity to progestin. In like manner, a low cytosol concentration of these steroid receptors appears to predict a good response to cytotoxic chemotherapy, as demonstrated in one study.Progestin and anti‐estrogen exert their anti‐neoplastic effect via an operative receptor mechanism in different ways, whereas cytotoxic chemotherapy acts by means not involving steroid receptors. It is therefore likely that a detailed characterization of the endocrine relations of the tumor by precise assay of ER and PR from the cytosol and nuclear fractions, together with determination of the end‐product of progestin action, 17β‐hydroxysteroid dehydrogenase, will further enhance the accuracy of individual a priori selection of the most efficacious chemotherapy available.