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

摘要: Tamoxifen is one of the most effective treatments for breast cancer through its ability to antagonize estrogendependent growth by binding estrogen receptors (ERs) and inhibiting epithelial cell proliferation. However, tamoxifen has estrogenic agonist effects in other tissues such as bone endometrium because liganded ER-activating target genes these different types. Several novel antiestrogen compounds have been developed that are also selective ER modulators (SERMs) but a reduced profile on gynecological tissues. These SERMs offer potential enhanced efficacy toxicity compared with tamoxifen. In advanced clinical data exist three first-generation (toremifene, droloxifene, idoxifene), which related triphenylethylene structure Phase II trials total 263 patients resistant tamoxifen, median objective response rate was only 5% (range, 0–15%), stable disease ≥6 months an additional 18% 9–23%). As first-line therapy cancer, 31% 20–68%) time progression 7 months. Randomized III toremifene idoxifene more than 1500 showed no significant difference Fewer structurally distinct second- third-generation (raloxifene, arzoxifene, EM-800, ERA-923), although similarly low 6% 0–14%) seen tamoxifen-resistant patients. It remains unclear whether any advantage exists over therapy. With emergence potent aromatase inhibitors (AIs) superior questions shifted (including SERMs) may be following failure AIs, merit combined AI/SERM The main SERM probably early stage-disease (adjuvant or prevention), side prove beneficial either AI. issue current sufficiently strong encourage further development.