Use of SERMs for the adjuvant therapy of early-stage breast cancer.

Tamoxifen was the first in a class of drugs now commonly referred to as selective estrogen receptor modulators or SERMs. SERMs exhibit tissue-specific estrogenic agonist/antagonist activity through their ability to bind to the estrogen receptor alpha (ER) protein and interact with coregulatory proteins, thereby modulating transcription of estrogen target genes. Since its first approval by the United States Food and Drug Administration (FDA) in 1977, tamoxifen has been found to (a) lower the risk of recurrence and death for women with early-stage hormone receptor-positive breast cancer, irrespective of menopausal and node status or use of adjuvant chemotherapy; (b) reduce the risk of invasive breast cancer following breast conservation in women with ductal carcinoma in situ (DCIS); and (c) reduce the risk of breast cancer in high-risk women. Toremifene is the only other SERM approved by the FDA for breast cancer treatment. However, it offers no clear clinical advantage over tamoxifen in the adjuvant or metastatic settings. Several other SERMs are in various phases of clinical development. In addition, strategies to combine SERMs with other endocrine therapy like ovarian suppression or aromatase inhibitors are active areas of investigations. At present, SERMs are recognized as the first targeted and relatively nontoxic medical therapy for women with high-risk or steroid hormone receptor-positive breast cancer.