Level 2: Mid-level evidence

Selective estrogen-receptor modulators (tamoxifen [Nolvadex, Soltamox], raloxifene [Evista]) have been shown to reduce the risk of breast cancer in postmenopausal women, but also have been associated with increased risk of venous thromboembolism and other serious adverse events (U.S. Preventive Services Task Force. Ann Intern Med. 2009;151:703-715). These risks have limited the use of these drugs for chemoprevention. A new trial suggests that the aromatase inhibitor exemestane (Aromasin) may reduce breast-cancer risk without serious adverse effects.

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A total of 4,560 postmenopausal women (mean age 63 years) were randomized to exemestane 25 mg daily vs. placebo (Gross PE et al.N Engl J Med. 2011; 364:2381-2391). All women had at least one 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 in 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 did the placebo group (32 women, 1.4%; number needed to treat=109). Annual incidence rates appeared stable (and lower with exemestane) for the first four years.

Data suggested a sharper increase in breast cancer rates in the placebo group from year four to year five (suggesting NNT=27 over five years), but only 159 women were followed to five 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 flushes, fatigue, sweating, insomnia, diarrhea, nausea, arthritis and joint and muscle pain were increased in the exemestane group.

All electronic documents accessed October 28, 2011.