Exemestane Reduces Breast Cancer Risk in High-Risk Postmenopausal Women
The list of drugs that have been shown to reduce a woman's chance of developing breast cancer can now be expanded from two to three. Clinical trial results presented at the 2011 American Society of Clinical Oncology (ASCO) annual meeting showed that the aromatase inhibitor exemestane (Aromasin®) — commonly used to treat early and advanced-stage breast cancer—substantially reduced the risk of invasive breast cancer in postmenopausal women at high risk of developing the disease.
Some researchers cautioned that 3 years of follow-up may not be long enough to determine the extent of any serious side effects, including osteoporosis, from long-term use of aromatase inhibitors in this patient population.
Despite the limited follow-up, the trial's principal investigator, Paul Goss, M.B. BCh, Ph.D., of Harvard Medical School, said the findings were enough to establish exemestane "as a new option for breast cancer prevention in postmenopausal women." All women older than 60, who by virtue of their age alone have an increased breast cancer risk, "should be made aware of these results," he continued.
Participants were randomly assigned to take exemestane or a placebo daily for 5 years. Overall, 11 women assigned to exemestane developed an invasive breast cancer, compared with 32 women who took the placebo. Exemestane use also led to statistically significant reductions in the development of DCIS, Dr. Goss said, and the invasive tumors that did develop in women taking exemestane were less aggressive than those in the placebo group.
Understanding the Side Effects
The data from the MAP.3 trial indicate that exemestane provides another option for risk reduction in the appropriate women, said Worta McCaskill-Stevens, M.D., of NCI's Division of Cancer Prevention (DCP). "But when thinking about prevention, women ask [about] the duration of use of the drug and [want] a clear understanding of its potential side effects," she cautioned.
Of particular concern is severe joint pain, or arthralgia, whose incidence has been relatively high in women being treated for cancer with aromatase inhibitors.
Several studies, however, have shown that women continue to experience the benefits of treatment after stopping aromatase inhibitors—a phenomenon known as a carry-over effect—and that they have fewer adverse events. The women who participated in MAP.3 will have to be followed to better assess the extent and significance of long-term side effects, especially osteoporosis, she stressed.
Victor Vogel, M.D., director of the cancer institute at Geisinger Health System in Danville, PA, who was involved in the tamoxifen and raloxifene prevention trials, called the risk reduction findings with exemestane "very impressive." Many of exemestane's side effects can be prevented and treated with monitoring, he explained.
Even if a woman stops taking exemestane for risk reduction because of side effects, Dr. Goss believes, the effort will have been worthwhile. "We feel comfortable that if a woman takes [exemestane] for 6 months or a year, she's gained benefit," he said.
Several clinical trials currently under way should provide more information about the safety and possible side effects of aromatase inhibitors when used for breast cancer risk reduction, explained Leslie Ford, M.D., of DCP.
The British IBIS-2 trial is comparing the aromatase inhibitor anastrazole with a placebo in women at high risk of breast cancer. And a U.S. trial being led by the National Surgical Adjuvant Breast and Bowel Project is comparing the aromatase inhibitor letrozole with tamoxifen in postmenopausal women with DCIS.
More Choices in the Clinic
As Dr. Vogel stressed, it's not medical oncologists but primary care physicians who would talk with women about their breast cancer risk and whether they should consider taking a drug for prevention. This group of clinicians, along with women themselves, needs to be educated about breast cancer prevention, he explained.
"We need to train primary care physicians about how to do risk assessment; how to counsel these patients," said Dr. Vogel. "And we need to ensure that reimbursement is available so that doctors get paid for taking the time to counsel their patients about preventive interventions."
Indeed, as Andrew Seidman, M.D., of Memorial Sloan-Kettering Cancer Center noted, unlike with blood pressure or cholesterol medicines, one cannot measure whether tamoxifen, raloxifene, or exemestane is having its intended preventive effect. "There's no feedback loop," he said, to let doctors and women know whether the drug is having the intended effect.
The patent for exemestane expired in 2010, and Pfizer, which manufactures the drug, has not said whether it will apply to the FDA to market exemestane for breast cancer risk reduction.