Exemestane Reduces Breast Cancer Risk for Postmenopausal Women

Chicago—A randomized, double-blind, placebo-controlled, phase 3 study presented in an oral abstract session at the ASCO meeting revealed that exemestane reduced the risk of invasive breast cancer by 65% in postmenopausal women who are at high risk for breast cancer. The median follow-up time was 3 years. Results of the MAP.3 (Mammary Prevention Trial.3) study were simultaneously published online in the New England Journal of Medicine [10.1056/NEJMoa1103507]. Paul E. Goss, MD, PhD, professor of medicine at Harvard Medical School and the trial’s lead author, said that exemestane could now be considered an alternative to selective estrogen receptor modulators (tamoxifen and raloxifene) in treating this subgroup of patients, although he said that further data are needed to determine whether exemestane is effective and safe in non-postmenopausal women. The US Food and Drug Administration (FDA) has approved tamoxifen and raloxifene to prevent breast cancer, but Dr. Goss said only an estimated 4% of women eligible to receive tamoxifen have agreed to take the drug because of rare but serious side effects such as blood clots or strokes. Exemestane is 1 of 3 FDA-approved aromatase inhibitors (AIs) that suppress estrogen and is intended for women who have experienced menopause and been treated with tamoxifen for 2 to 3 years. Dr. Goss said the researchers chose to examine exemestane rather than the other AIs because it causes less bone loss. “I think there’s a new and highly effective way to treat breast cancer,” Dr. Goss said. “It seems there’s a cumulative benefit with no downside.… This result will have widespread implications in discussions between doctors and women.” In the study, 4560 patients from the United States, Canada, Spain, and France were randomized in a 1:1 ratio to receive 25 mg of exemestane daily for 5 years or placebo daily for 5 years. Enrollment occurred between February 11, 2004, and March 23, 2010, and the treatment and placebo groups had similar baseline characteristics: the median age was approximately 63 years, approximately 93% of patients were white, and the median body mass index was approximately 28. The National Cancer Institute of Canada Clinical Trials Group coordinated and led the study. Eligibility criteria included postmenopausal women ≥35 years of age who had ≥1 of the following risk factors: ≥60 years of age; Breast Cancer Risk Assessment Tool (Gail model) >1.66%; prior atypical ductal or lobular hyperplasia or lobular carcinoma in situ; or ductal carcinoma in situ (DCIS) with prior mastectomy. Patients were excluded if they carried the BRCA1 or BRCA2 gene, had a prior DCIS with lumpectomy, or had a history of breast cancer or other malignancies. There were 32 invasive breast cancers in the placebo group (annual incidence rate of 0.55%; 95% confidence interval [CI], 0.08%-0.30%) compared with 11 (annual incidence rate of 0.19%; 95% CI, 0.36%-0.73%) in the exemestane group (hazard ratio [HR], 0.35; 95% CI, 0.18-0.70; P=.002). When combining invasive and preinvasive breast cancers, there were 44 events in the placebo group (annual incidence rate of 0.77%) compared with 20 (annual incidence rate of 0.35%) in the exemestane group (HR, 0.47; 95% CI, 0.27-0.79; P=.004). In the exemestane group, 88% of women experienced an adverse event (AE) compared with 85% of the patients in the placebo group (P=.003). Patients taking exemestane had a statistically significant increase in hot flashes, fatigue, insomnia, diarrhea, nausea, arthritis, joint pain, and muscle pain. However, there were no significant differences between the groups in terms of serious AEs such as cardiovascular disease, clinical skeletal fractures, osteoporosis, and other malignancies.