Approximately 230,480 new cases of breast cancer were diagnosed in the United States in 2011.1 Improved methods of prevention are needed. There are only two Food and Drug Administration approved pharmacologic options - tamoxifen and raloxifene - for the prevention of breast cancer in high risk, postmenopausal women. The MAP.3 trial provides new information about the aromatase inhibitor exemestane.2 It establishes that exemestane can be used effectively and safely to reduce the risk of invasive breast cancer in postmenopausal women.
Goss and colleagues recently published the results of the MAP.3 study. It was a randomized, placebo-controlled, double blind trial that compared the aromatase inhibitor exemestane to placebo. The trial was conducted in Canada, United States, Spain, and France. It included postmenopausal women 35 years or older who had at least one of the following risk factors: 60 years of age or older; Gail 5-year risk score greater than 1.66% (chances in 100 of invasive breast cancer developing in 5 years); prior atypical ductal or lobular hyperplasia or lobular carcinoma in situ; or ductal carcinoma in situ with mastectomy. Carriers of the breast cancer susceptibility gene 1 (BRCA1) and BRCA2 mutations were excluded. The primary outcome was incidence of invasive breast cancer. The planned duration of therapy was 5 years.
A total of 4,560 postmenopausal women were randomly assigned to one of two treatment groups: 25mg of exemestane or placebo. The two groups were well balanced for race, body mass index, and breast cancer risk factors. Approximately 40% of patients had a Gail score for 5-year breast cancer risk greater than 1.66%; median Gail score was 2.3% for both groups. Pretreatment bone mineral density, prior history of clinical fractures, and cardiovascular risk factors were similar between study groups.
At a median follow-up of three years, 43 cases of invasive breast cancer were diagnosed; 11 in the exemestane group and 32 in the placebo group (annual incidence, 0.19% with exemestane vs. 0.55% with placebo; p value 0.002), which is a 65% reduction in the exemestane group. There were similar trends seen for ductal carcinoma in situ (DCIS), but they were not statistically significant. There were a total of 23 cases of DCIS; 9 in the exemestane group and 14 in the placebo group (annual incidence, 0.16% with exemestane vs. 0.24% with placebo; p value 0.31). Adverse events such as arthritis, hot flashes, fatigue, and sweating were common in all women, but slightly more frequent in the exemestane group. Based on the surveys taken by the subjects, these symptoms did not appear to affect self-report of overall health-related quality of life. Secondary end point toxicities, including new diagnosis of osteoporosis, cardiovascular events, hypercholesteremia, clinical fractures, or other solid tumors, were not significantly different between the two groups.
The authors concluded that exemestane significantly reduced invasive breast cancers in postmenopausal women who were at a moderately increased risk for breast cancer compared to placebo. Exemestane was associated with no serious toxic effects and only minimal changes in ...