Raloxifene: Selective estrogen receptor modulator approved by FDA for reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis or at high risk for invasive breast cancer

Raloxifene was approved on September 13, 2007, for the additional indication of the reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis and in postmenopausal women at high risk for invasive breast cancer.

Key Points

Raloxifene exerts its biologic effects by binding to estrogen receptors and either activating or blocking specific estrogenic pathways. This agent was approved previously for the treatment and prevention of osteoporosis in postmenopausal women. Raloxifene was approved on September 13, 2007, for the additional indication of the reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis and in postmenopausal women at high risk for invasive breast cancer.

Efficacy. The efficacy of raloxifene in reducing the risk of invasive breast cancer in postmenopausal women with osteoporosis was evaluated as a secondary safety end point in a randomized, placebo-controlled, double-blind, multinational osteoporosis treatment trial in postmenopausal women. After 4 years of therapy, women treated with raloxifene 60 mg/d demonstrated a 62% reduced incidence of all breast cancers versus placebo-treated patients (HR=0.38; 95% CI, 0.22–0.67). The incidence of invasive breast cancer was reduced by 71% among patients treated with raloxifene versus placebo (absolute RR=3.1 per 1,000 women-y), a reduction due primarily to an 80% reduction in the incidence of estrogen receptor (ER)-positive invasive breast cancer among patients treated with raloxifene versus placebo. In a 4-year follow-up, patients treated with raloxifene 60 mg/d demonstrated a 56% reduction in the incidence of invasive breast cancer versus placebo-treated patients (absolute RR=3.0 per 1,000 women-y), a reduction due primarily to a 63% reduction in the incidence of ER-positive invasive breast cancer among patients treated with raloxifene versus placebo. A randomized, placebo-controlled, double-blind, multinational study assessed the efficacy of raloxifene in reducing the risk of invasive breast cancer in postmenopausal women at increased risk for coronary events. Raloxifene 60 mg/d reduced the incidence of invasive breast cancer by 44% versus placebo (absolute RR=1.2 per 1,000 women-y), a reduction due primarily to a 55% reduction in the incidence of ER-positive invasive breast cancer among patients treated with raloxifene versus placebo (absolute RR=1.2 per 1,000 women-y). A randomized, double-blind trial assessed the efficacy of raloxifene 60 mg/d versus tamoxifen 20 mg/d over 5 years in reducing the risk of invasive breast cancer in postmenopausal women at high risk for invasive breast cancer. Raloxifene was not demonstrated to be superior to tamoxifen in this patient population (incidence of invasive breast cancer: raloxifene, 4.4 per 1,000 women per y; tamoxifen, 4.3 per 1,000 women per y).

Safety. Raloxifene-treated patients are at an increased risk of venous thromboembolism. Superficial thrombophlebitis has also been reported in raloxifene-treated patients. In clinical trials, women with documented coronary heart disease or at increased risk for coronary events had an increased risk of death caused by stroke after raloxifene treatment. Women who have experienced marked hypertriglyceridemia when treated with oral estrogen or estrogen plus progestin may experience increased triglyceride levels during raloxifene treatment. The most common adverse events associated with raloxifene treatment for the reduction in risk of invasive breast cancer include peripheral edema, muscle spasms/ leg cramps, hot flashes, venous thromboembolic events, and cholelithiasis.