PMID: 11916228Mar 28, 2002Paper

Endocrine manipulation in advanced breast cancer: recent advances with SERM therapies

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
S Johnston

Abstract

Tamoxifen is one of the most effective treatments for breast cancer through its ability to antagonize estrogen-dependent growth by binding estrogen receptors (ERs) and inhibiting breast epithelial cell proliferation. However, tamoxifen has estrogenic agonist effects in other tissues such as bone and endometrium because of liganded ER-activating target genes in these different cell types. Several novel antiestrogen compounds have been developed that are also selective ER modulators (SERMs) but that have a reduced agonist profile on breast and gynecological tissues. These SERMs offer the potential for enhanced efficacy and reduced toxicity compared with tamoxifen. In advanced breast cancer clinical data exist for three first-generation SERMs (toremifene, droloxifene, idoxifene), which are related to the triphenylethylene structure of tamoxifen. In Phase II trials in a total of 263 patients resistant to tamoxifen, the median objective response rate to these SERMs was only 5% (range, 0-15%), with stable disease for > or =6 months in an additional 18% (range, 9-23%). As first-line therapy for advanced breast cancer, the median response rate was 31% (range, 20-68%) with a median time to progression of 7 months. Randomized Phase III t...Continue Reading

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