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However, these drugs also have many estrogenic effects depending on the tissue and gene, and they are more appropriately called selective estrogen receptor modulators (SERMs). SERMs bind ER, alter receptor conformation, and facilitate binding of coregulatory proteins that activate or repress transcriptional activation of estrogen target genes. Theoretically, SERMs could be synthesized that would exhibit nearly complete agonist activity on the one hand or pure antiestrogenic activity on the other. Depending on their functional activities, SERMs could then be developed for a variety of clinical uses, including prevention and treatment of osteoporosis, treatment and prevention of estrogen-regulated malignancies, and even for hormone replacement therapy. Tamoxifen is effective in patients with ER-positive metastatic breast cancer and in the adjuvant setting. The promising role for tamoxifen in ductal carcinoma-in-situ or for breast cancer prevention is evolving, and its use can be considered in certain patient groups. Other SERMs are in development, with the goal of reducing toxicity and\/or improving efficacy, and future agents have the potential of providing a new paradigm for maintaining the health of women.<\/jats:p>","DOI":"10.1200\/jco.2000.18.17.3172","type":"journal-article","created":{"date-parts":[[2017,2,24]],"date-time":"2017-02-24T09:34:32Z","timestamp":1487928872000},"page":"3172-3186","source":"Crossref","is-referenced-by-count":274,"title":["Selective Estrogen Receptor Modulators: Structure, Function, and Clinical Use"],"prefix":"10.1200","volume":"18","author":[{"given":"C. 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