Exemestane Effective for Primary Prevention of Breast Cancer

CHICAGO—Exemestane appears to be a good alternative to tamoxifen for prevention of breast cancer in postmenopausal women, according to results of the randomized, placebo-controlled MAP.3 trial. Exemestane reduced the risk of a first invasive breast cancer by 65% in healthy postmenopausal women with risk factors for breast cancer, and also reduced the risk of known breast cancer precursor lesions, including ductal carcinoma in situ, lobular carcinoma in situ, atypical ductal hyperplasia, and atypical lobular hyperplasia, which would suggest further reductions in invasive cancers as time goes by. Exemestane did not increase the incidence of serious side effects, including osteoporosis and clinical fracture, cardiovascular events, and second malignancies, or treatmentrelated deaths, compared with placebo.

Although tamoxifen is approved by the US Food and Drug Administration for prevention of breast cancer, only about 4% of eligible women actually take the drug, explained lead author Paul Goss, MD, director of breast cancer research, Harvard Medical School and Massachusetts General Hospital in Boston. Tamoxifen carries serious, but relatively rare, risks of venous thromboembolism and endometrial cancer. Unlike tamoxifen, exemestane is not approved for prevention of breast cancer. The drug is about to go off-patent, and it is not clear whether Pfizer will try to file for the prevention indication.

“It is extraordinary that we can reduce the incidence of breast cancer by 65%. That is a massive benefit. In our opinion, exemestane represents a new option for consideration for breast cancer prevention in postmenopausal women who meet the criteria of the MAP.3 trial. This study provides a rationale for wider implementation of preventive use of exemestane,” Goss stated.

Between 2004 and 2010, the study enrolled 4560 postmenopausal women older than age 37 (median age, 62 years) with at least 1 risk factor for breast cancer (age 60 or older, Gail score >1.66%, prior atypical ductal hyperplasia, and atypical lobular hyperplasia). At baseline, median Gail score was 2.3% and average body mass index was 28 kg/m2. About half of participants were older than 50 years, 40% had a Gail score >1.66%, and 11% had prior intraepithelial neoplasia.

During the 3-year follow-up, 11 cases of breast cancer were diagnosed in the exemestane arm compared with 32 in the placebo arm. The benefit of exemestane was in the reduction of estrogen receptor–positive tumors (7 in the exemestane arm vs 27 in the placebo arm) and in HER2-negative tumors (10 vs 26, respectively).

The superiority of exemestane to placebo was evident across all risk groups, including Gail score, age, body mass index, prior lobular carcinoma in situ, and prior ductal carcinoma in situ.

Side effects that were increased with exemestane included hot flashes, fatigue, insomnia, gastrointestinal effects, and arthritis. Hot flashes occurred in 40% of women treated with exemestane and 32% of those in the placebo group. The incidence of bone fracture, osteoporosis, cardiovascular events, and other malignancies was similar in both arms.

“The elephant in the kitchen [in women at risk for breast cancer] is prophylactic mastectomy. Exemestane is now another treatment option for these women,” said Andrew Seidman, MD, of the Breast Cancer Medicine Service, Memorial Sloan-Kettering Cancer Center in New York City. Seidman chaired the press conference where these data were presented.