Steroidal and nonsteroidal oestrogen antagonists in breast cancer: basic and clinical appraisal.

Endogenous sex hormones, such as oestrogens, control the development and growth of breast carcinoma. Blocking the binding between the steroid 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-oestrogen tamoxifen has so far been the standard compound for endocrine treatment of breast cancer. Nevertheless, it forms a complex with the oestrogen receptor which gives rise to a range of biopharmacological events, ranging from full oestrogen antagonism to partial agonism. Moreover, its use is limited by the possible onset of drug resistance in many patients. In spite of these restrictions, tamoxifen has proved to be very helpful as a starting point for the development of new, more efficacious 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, pharmacology and clinical evaluation.