STEROIDAL AND NONSTEROIDAL ESTROGEN ANTAGONISTS IN BREAST-CANCER - BASIC AND CLINICAL APPRAISAL

Endogenous sex hormones, such as oestrogens, control the development a nd growth of breast carcinoma. Blocking the binding between the steroi d hormone and its receptor using anti-oestrogenic compounds is one of the possible ways of impeding the action of oestrogens at the level of their target tissues. The nonsteroidal, triphenylethylenic, anti-oest rogen tamoxifen has so far been the standard compound far endocrine tr eatment of breast cancer. Nevertheless, it forms a complex with the oe strogen receptor which gives rise to a range of biopharmacological eve nts, ranging from full oestrogen antagonism to partial agonism. Moreov er, its use is limited by the possible onset of drug resistance in man y patients. In spite of these restrictions, tamoxifen has proved to be very helpful as a starting point for the development of new, more eff icacious compounds. In this article, Roberto Favoni and Alessandra de Cupis review and discuss tamoxifen, several of Its derivatives and the steroidal-like anti-oestrogens in terms of laboratory development, ph armacology and clinical evaluation.