Estrogens work along with genetic changes to promote the development and growth of breast cancers. Because estrogenic hormones act via the estrogen receptors (ERs), ER-α and ER-β, and the ER is present in more than half of breast tumors, this receptor has been the most widely targeted protein in breast cancer therapy. The presence of the ER in breast tumors predicts improved disease-free survival and response to selective ER modulators (SERMs), such as tamoxifen, or other forms of endocrine therapy. Suppression of ER activity by SERMs has proven to be a great benefit in the treatment of breast cancers and also in the prevention of breast cancer in women at high risk for the disease. The Study of Tamoxifen and Raloxifene trial comparing tamoxifen versus raloxifene effectiveness in breast cancer prevention is currently under way. To understand the balance of beneficial and undesirable effects of SERMs and to optimize their effectiveness, current investigations seek to characterize the genes activated or suppressed by these agents. Elucidation of the gene networks and cell signaling pathways under estrogen and SERM regulation and a clearer definition of the respective roles of ER-α and ER-β and their coregulators in the actions of selective ER ligands, should enable the identification of new gene targets for therapeutic intervention and the development of novel drugs for the optimal treatment and prevention of breast cancer.
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