Volume 355: 190-192 July 13, 2006 Number 2
Risk–Benefit Profiles of Raloxifene for Women
Marcia L. Stefanick, Ph.D.
During the past decade, considerable scientific, clinical, and public interest in the benefits and risks of postmenopausal estrogen therapy has focused attention on selective estrogen-receptor modulators (SERMs). These act as estrogen agonists in some tissues and antagonists in others because of specific actions on at least two distinct estrogen receptors, the proportions of which differ across tissues. As such, SERMs have held the promise of conferring benefits similar to those associated with estrogen therapy, including a reduced risk of osteoporosis, while simultaneously reducing estrogen-related risks (e.g., invasive breast cancer). The once widely held belief that estrogen therapy was cardioprotective1 also generated hope that a SERM might prevent coronary heart disease (CHD).
The Breast Cancer Prevention Trial of the National Surgical Adjuvant Breast and Bowel Project provided evidence in 1998 that a SERM, tamoxifen, could reduce breast cancer risk in a cohort of 13,388 women at increased risk for breast cancer2. Tamoxifen significantly reduced the risk of invasive breast cancer and, in particular, tumors with positive estrogen-receptor status (relative risk reductions, 49 percent and 69 percent, respectively). Tamoxifen also reduced the risk of fractures, though not significantly. However, it was associated with significantly increased risks of endometrial cancer, stroke, pulmonary emboli, deep-vein thrombosis, and cataracts, primarily in women 50 years of age or older2.