Laboratoire de recherche en oncologie, Centre Alexis-Vautrin, avenue de Bourgogne, 54511 Vandœuvre-les-Nancy, France.
Tamoxifen is the most currently used antiestrogen in the endocrine treatment of breast cancer. However, despite a small proportion of estrogen receptor positive tumors presenting de novo resistance to treatment, numerous tumors develop acquired resistance after a first phase of response. Many mechanisms have been proposed, but none could be identified as a real explanation of these phenomena of resistance. The hypotheses suggested are related to the series of events implied in the transduction of the signal following the ligand binding to estrogen receptor and concerning several levels: (1) loss or mutation of the estrogen receptor; (2) modification in estrogen receptor associated parameters; (3) alteration in the estrogen response element; (4) high levels of antiestrogen binding sites; (5) alteration of metabolism or availability of tamoxifen. The tamoxifen resistance certainly concerns several of these mechanisms. Therefore, it is necessary to go on studying these mechanisms and to elucidate the connections existing between all of them.