Exemestane May Reduce Risk of Invasive Breast Cancer in At-Risk Postmenopausal Women

DynaMed Weekly Update - Volume 6, Issue 26

Selective estrogen-receptor modulators (tamoxifen, raloxifene) have been shown to reduce the risk of breast cancer in postmenopausal women, but have also been associated with increased risk of venous thromboembolism and other serious adverse events (Ann Intern Med 2009 Nov 17;151(10):703). These risks have limited the use of these drugs for chemoprevention. A new trial suggests that the aromatase inhibitor exemestane may reduce breast cancer risk without serious adverse effects (level 2 [mid-level] evidence). A total of 4,560 postmenopausal women (mean age 63 years) were randomized to exemestane 25 mg daily vs. placebo. All women had at least 1 risk factor for invasive breast cancer, including age ? 60 years, Gail risk score > 1.66%, prior atypical ductal or lobular hyperplasia, lobular carcinoma in situ on breast biopsy, or prior ductal carcinoma in situ treated with mastectomy.

Median treatment duration was 10.2 months in the exemestane group and 14.2 months in the placebo group. Study medication was discontinued early for reasons other than the development of breast events in 27% for exemestane and 21% for placebo. At median follow-up of 35 months, the exemestane group had significantly fewer women with invasive breast cancer (11 women, 0.48%) than the placebo group (32 women, 1.4%) (NNT 109). Annual incidence rates appeared stable (and lower with exemestane) for the first 4 years. Data suggested a sharper increase in breast cancer rates in the placebo group from year 4 to year 5 (suggesting NNT 27 over 5 years), but only 159 women were followed to 5 years. There were no significant differences in rate of ductal carcinoma in situ, new osteoporosis or cardiovascular events, or quality of life scores. Rates of minor adverse events including hot flashes, fatigue, sweating, insomnia, diarrhea, nausea, arthritis, and joint and muscle pain were increased in the exemestane group (N Engl J Med 2011 Jun 23;364(25):2381).

For more information, see the Chemoprevention of breast cancer topic in DynaMed.