Raloxifene: A Selective Estrogen Receptor Modulator for Reducing the Risk of Invasive Breast Cancer in Postmenopausal Women

Abstract

Raloxifene hydrochloride is a selective estrogen receptor modulator that has antiestrogenic effects on breast and endometrial tissue and estrogenic effects on bone, lipid metabolism and blood clotting. Tamoxifen is the prototypical selective estrogen receptor modulator and reduces the risk of both in situ and invasive breast cancers by half when compared with placebo. The limitations on the use of tamoxifen for breast cancer risk reduction relate to its well-known, but rare, side effects. A number of clinical trials have established the benefit of raloxifene on osteoporosis and fracture. Raloxifene significantly improves serum lipids and serum markers of cardiovascular disease risk, but has no significant effect on the risk of primary coronary events. In several osteoporosis trials and the Raloxifene Use for The Heart (RUTH) trial, raloxifene decreased the risk of estrogen receptor-positive breast cancer by 44-90%. In the Study of Tamoxifen And Raloxifene (STAR) trial, the effect of raloxifene on invasive breast cancer was equivalent to that of tamoxifen, with more favorable effects on uterine malignancy and clotting events. Symptomatic side effects are acceptable. In total, the available data indicate that raloxifene represents an acceptable alternative to tamoxifen for the reduction of the risk of postmenopausal breast cancer in high-risk women. The potential market for a compound shown to reduce the risk of breast cancer in postmenopausal women who are at increased risk for breast cancer is more than 10 million women in the USA alone.

Terpenoids and breast cancer chemoprevention

“…Raloxifene is another SERM that has been shown clinically and experimentally to be antiestrogenic in the breast and uterus. Raloxifene hydrochloride is a SERM that has anti-estrogenic effects on breast and endometrial tissue and estrogenic effects on bone, lipid metabolism, and blood clotting [157]. It is a benzothiophene with characteristics similar to but distinct from the triphenylethylene SERMs such as tamoxifen.…”

Effect of selective estrogen receptor modulators on metabolic homeostasis

“…The second-generation SERMs were developed to overcome the adverse effect of tamoxifen on endometrial proliferation. Raloxifene, which retains anti-estrogenic activity in breast tissue [9] and exhibits estrogenic activity in bone, can also prevent osteoporosis [10]. The emerging third-generation SERM, bazedoxifene (BZA), is used to prevent osteoporosis in postmenopausal women without raising the safety concerns related to endometrium and breast tissue [11,12].…”

Reducing the Risk of Endometrial Cancer in Patients Receiving Selective Estrogen Receptor Modulator (SERM) Therapy

“…Raloxifene has the ability to bind to and activate the estrogen receptor while exhibiting tissue-specific effects distinct from estradiol (Vogel 2007). As a result, raloxifene was specifically developed to maintain beneficial estrogenic activity on bone and lipids and antiestrogenic activity on endometrial and breast tissue.…”