Until recently, women at risk for breast cancer have had 2 pharmacologic options to reduce their risk— tamoxifen (Nolvadex) and raloxifene (Evista). Now a third option has been shown effective, the aromatase inhib - itor exemestane (Aromasin).
Five years of treatment with exemestane significantly reduced invasive and preinvasive breast cancers in postmenopausal women at increased risk for the disease in the Canadian National Cancer Institute of Canada Clinical Trials Group MAP.3 trial, presented at ASCO 2011 by Paul Goss, MD, PhD, Harvard Medical School.
Tamoxifen and raloxifene are associated with the potential for rare but serious side effects, including venous thromboembolism and endometrial cancer, and many women avoid these drugs for this reason. “Our study not only showed an impressive reduction in breast cancers but also an excellent side effect profile,” said Dr Goss.
Exemestane is currently indicated for adjuvant endocrine treatment but is not approved by the US Food and Drug Administration for the prevention of breast cancer. Because of the drug’s more favorable effects on bone, compared with other aromatase inhibitors, exemestane was selected for evaluation in a breast cancer prevention trial. The study is the first randomized trial to assess an aromatase inhibitor for breast cancer prevention in healthy women.
The MAP.3 trial enrolled 4560 postmenopausal women with at least 1 risk factor that increased their chances of developing breast cancer (although none carried the BRCA mutation). Approximately half of the population was considered at risk simply because they were aged ≥60 years.
The women were randomly as - signed to 5 years of exemestane 25 mg daily or to placebo. After a median follow- up of 3 years, 11 breast cancers occurred in the exemestane group compared with 32 in the placebo group, representing an annual incidence of 0.19% versus 0.55%, respectively (P = .002). This translated into a 65% reduction of invasive cancers with exemestane, Dr Goss reported.
The protective effect was most striking among the estrogen receptor–positive subset, who experienced a 73% relative risk reduction (P = .008). There were also reductions in preinvasive breast cancer and ductal carcinoma in situ, as well as precursor lesions such as atypical ductal hyperplasia.
Serious toxicities were not seen over 3 years, although significantly more women who received exemestane reported bodily pain than those receiving placebo (46% vs 41%, respectively; P <.001).
The effect appeared to be more durable than what is observed with tamoxifen, Dr Goss noted. In addition, fewer women taking exemestane—26 compared with 95 women taking tamoxifen (in other studies)—must be treated to prevent 1 case of breast cancer over 5 years, he said.
“The findings from MAP.3 indicate that exemestane is a promising new option for preventing breast cancer in menopausal women,” Dr Goss commented. Although exemestane has been an expensive hormonal therapy, its patent has expired and “the cost is plummeting,” he said, predicting the cost of treat ment will soon be “comparable to tamoxifen.”
A Possible Paradigm Shift in the Prevention of Breast Cancer
“MAP.3 provides a paradigm shift for breast cancer prevention. Avoiding breast cancer with manageable toxicity is possible today,” said Andrea De Censi, MD, of the E.O. Ospedali Galliera in Genoa, Italy, who was invited to discuss the findings.
Although tamoxifen remains the favored preventive approach for atrisk premenopausal women, exemestane may become a preferred option in the postmenopausal group, Dr De Censi said.