[Recent data on the mechanism of action of synthetic antiestrogens].

Synthetic antiestrogens such as Tamoxifen (Nolvadex) are currently used to treat postmenopausal breast cancer. Their mechanism of action is reviewed at the cellular and molecular level, through data of the literature and the current view of the author. Synthetic antiestrogens are mostly acting directly on breast cancer cells by interacting with the estrogen receptor (RE). They prevent estrogen action by competing with estrogens on the cytosol RE. The resulting complex is partially activated resulting in its nuclear localisation and a partial and dissociated stimulation of the expression of estrogen responsive genes. The explanation of the antitumoral effect of these drugs is more controversial, since the regulation of cell proliferation is not only due to estrogens but also to other hormones and factors. The antiestrogens can therefore block cancer cell growth by inhibiting estrogen action, or by a RE medicated cytotoxic effect and/or by any other mechanism involving indirect effects, or binding to other proteins than the RE.