Chicago, IL—Exemestane (Aromasin) appears to be a good alternative to tamoxifen (Nolvadex) for prevention of breast cancer in postmenopausal women, according to results of the randomized, placebo-controlled MAP.3 trial reported at ASCO 2011.
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 any serious side effects compared with placebo, including second malignancies, or treatment-related deaths.
Exemestane is currently indicated for the adjuvant treatment of post-menopausal women with estrogenreceptor– positive early breast cancer. It is not indicated for the prevention of breast cancer.
Although tamoxifen is approved by the US Food and Drug Administration (FDA) for prevention of breast cancer, only approximately 4% of eligible women actually take this drug, said lead author Paul Goss, MD, PhD, Harvard Medical School and Massachusetts General Hospital. Tamoxifen carries serious but relatively rare risks of venous thromboembolism and endometrial cancer. In contrast, exemestane is not FDA approved for the prevention of breast cancer. The drug is about to go off patent, and it is not clear whether its manufacturer will 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 of breast cancer prevention for postmenopausal women who meet the criteria of the MAP.3 trial. This study provides a rationale for wider implementation of preventive use of exemestane,” Dr Goss stated.
Between 2004 and 2010, MAP.3 enrolled 4560 postmenopausal women aged ≥37 years (median age, 62 years) with at least 1 risk factor for breast cancer (age ≥60 years, Gail score >1.66%, previous atypical ductal hyperplasia, and atypical lobular hyperplasia). At baseline, median Gail score was 2.3% and average body mass index (BMI) was 28 kg/m2. Approximately 50% of the participants were aged >50 years, 40% had a Gail score >1.66%, and 11% had a history of 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. Exemestane significantly reduced the incidence of estrogen-receptor–positive tumors—7 in the exemestane arm versus 27 in the placebo arm—and in HER2-negative tumors (10 and 26, respectively).
The superiority of exemestane to placebo was evident across all risk groups, including Gail score, age, BMI, prior lobular carcinoma in situ, and prior ductal carcinoma in situ.
Side effects that were higher with exemestane compared with placebo 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 groups. 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, Memorial Sloan-Kettering Cancer Center, NY, who chaired the press conference where these data were presented.
