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  • Title: Treatment of Postmenopausal Breast Cancer with Selective Estrogen Receptor Modulators (SERMs).
    Author: Lewis-Wambi JS, Jordan VC.
    Journal: Breast Dis; ; 24():93-105. PubMed ID: 16917142.
    Abstract:
    Endocrine therapy that targets the estrogen receptor (ER) is a standard of care for the treatment of postmenopausal women with ER-positive breast cancer. The selective ER modulator (SERM) tamoxifen has been in use for the treatment of advanced breast cancer for more than 30 years and is currently a treatment option for all stages of ER-positive disease. Tamoxifen blocks the action of estrogen by binding to the ER, and possesses both ER-agonist and antagonist properties. Unfortunately, long-term use of tamoxifen is associated with several important concerns including an increased risk of endometrial cancer and thromboembolic complications. In addition, many patients who initially respond to tamoxifen eventually relapse with resistant disease. New treatment approaches are therefore required. A number of alternative SERMs have been tested as substitutes for tamoxifen. These include; toremifene, droloxifene, idoxifene, and keoxifene. Unfortunately, the SERMs have not proved to be more effective than tamoxifen for the treatment of advanced breast cancer and have shown a high level of cross-resistance with tamoxifen. The subsequent development of the aromatase inhibitors (AIs) is an important therapeutic advance by creating a "no estrogen" environment. Another approach is the development of pure antiestrogens. Fulvestrant is a novel ER antagonist that destroys the ER and its signaling pathway and is not associated with tamoxifen-like agonist effects. It produces high response rates compared with other SERMs and is not cross-resistant to tamoxifen or aromatase inhibitors and is equally as effective as the AI anastrozole in the treatment of postmenopausal women with advanced breast cancer who have progressed on prior adjuvant tamoxifen therapy. This review article discusses the significant and continuing value of SERMs for the treatment of postmenopausal ER-positive breast cancer.
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