Tamoxifen and raloxifene reduced the incidence of invasive breast cancer and fractures by 7 to 9 cases in 1,000 women over 5 years compared with placebo, but not without side effects, concluded a review by the U.S. Preventive Services Task Force.
There was an increased incidence of thromboembolic events, the review concluded. Also, tamoxifen was more effective than raloxifene, but also increased the incidence of endometrial cancer and cataracts.
Seven good- and fair-quality trials were reviewed, and results appeared in the April 16 edition of Annals of Internal Medicine.
New results from STAR (Study of Tamoxifen and Raloxifene) showed that tamoxifen reduced breast cancer incidence more than raloxifene by 5 cases in 1,000 women. Neither reduced breast cancer-specific or all-cause mortality. Both reduced the incidence of fractures, but tamoxifen increased the incidence of thromboembolic events more than raloxifene by 4 cases in 1,000 women.
Specifically, placebo-controlled trials showed a reduction of invasive breast cancer for tamoxifen (risk ratio [RR], 0.70; 95% confidence interval [CI], 0.59 to 0.82; 4 trials; 7 cases in 1,000 women over 5 years) and raloxifene (RR, 0.44; CI, 0.27 to 0.71; 2 trials; 9 cases in 1,000 women). STAR also showed that more women receiving raloxifene had breast cancer than those receiving tamoxifen (RR for raloxifene, 1.24; CI, 1.05 to 1.47; 5 cases in 1,000 women over 5 years).
Placebo-controlled trials also showed that raloxifene reduced incidence of vertebral fractures (RR, 0.61; CI, 0.54 to 0.69; 2 trials; 7 cases in 1,000 women) and tamoxifen reduced incidence of nonvertebral fractures (RR, 0.66; CI, 0.45 to 0.98; 1 trial; 3 cases in 1,000 women). STAR showed that tamoxifen and raloxifene had similar effects on incidence of vertebral fractures.
Thromboembolic event incidence was increased for tamoxifen (RR, 1.93; CI, 1.41 to 2.64; 4 trials; 4 cases in 1,000 women) and raloxifene (RR, 1.60; CI, 1.15 to 2.23; 2 trials; 7 cases in 1,000 women) compared with placebo. STAR showed that raloxifene caused fewer events than tamoxifen in STAR (RR, 0.75; CI, 0.60 to 0.93; 4 cases in 1,000 women). Coronary heart disease event or stroke incidence was not increased in placebo-controlled trials and did not differ in STAR.
Tamoxifen caused more cases of endometrial cancer (RR, 2.13; CI, 1.36 to 3.32; 3 trials; 4 cases in 1,000 women) and was related to more benign gynecologic conditions; surgical procedures, including hysterectomy; and uterine bleeding than placebo. Raloxifene did not increase risk for endometrial cancer or uterine bleeding. In STAR, raloxifene caused fewer cases of endometrial cancer (RR, 0.55; CI, 0.36 to 0.83; 5 cases in 1,000 women), hyperplasia, and procedures than tamoxifen.
Women receiving tamoxifen had more cataract surgeries than those receiving placebo in one trial. Raloxifene did not increase risk for cataracts or cataract surgery compared with placebo and caused fewer cataracts than tamoxifen in STAR (RR, 0.80; CI, 0.72 to 0.95; 15 cases in 1,000 women).
The most common side effects among studies were vasomotor symptoms and vaginal discharge, itching, or dryness for tamoxifen and vasomotor symptoms and leg cramps for raloxifene. In STAR, raloxifene users reported more musculoskeletal problems, dyspareunia and weight gain, whereas tamoxifen users had more gynecologic problems, vasomotor symptoms, leg cramps and bladder control symptoms.
"Despite previous recommendations to identify women at increased risk for breast cancer and offer risk-reducing medications, use is low in the United States," the authors wrote. "It is not clear how to identify candidates for therapy. Although the trials indicate broad benefit, subgroup analysis and decision models suggest that high-risk women, particularly those who had hysterectomies, may derive the most benefit with the least harms."