Drug Resistance to Antiestrogens

Tamoxifen (Nolvadex®) (Fig. 1), a nonsteroidal antiestrogen, is the endocrine treatment of choice for all stages of breast cancer. The drug has ten million women years of clinical experience and is described by the World Health Organization (WHO) as an essential treatment for breast cancer. The clinical pharmacology of tamoxifen has been studied in great detail because it is continuing to be tested as a preventive for breast cancer in high-risk women (1). This strategy is based on three important facts. Firstly, tamoxifen prevents rat mammary carcinogenesis (2,3). Secondly, tamoxifen reduces the incidence of contralateral breast cancer (4) and thirdly, when the preliminary studies were started in 1986 (5), tamoxifen was believed to have a low incidence of side effects (6).