ASCO 2011: Exemestane significantly reduces risk of invasive breast cancer in high-risk, postmenopausal women

June 2011 A large randomized double-blind phase III trial led by Canada's NCIC Clinical Trials Group (NCIC CTG) has shown that in postmenopausal women who are at increased risk of developing breast cancer, the aromatase inhibitor (AI) Exemestane reduces this risk by 65 percent compared with placebo.

"The potential public health impact of these findings is important. World-wide it is estimated that 1.3 million women are diagnosed with breast cancer each year and nearly 500,000 women die of the disease. Results from the MAP.3 trial indicate that Exemestane is a promising new way to prevent breast cancer in menopausal women most commonly affected with breast cancer," said Paul E. Goss, MD, PhD, lead study author and professor of medicine at Harvard Medical School and Massachusetts General Hospital in Boston, MA.

"The reduction in breast cancers of 65 percent we demonstrated was exactly in line with our expectations," Dr. Goss continued. "The numbers of tumours are small but there also appeared to be fewer of the more aggressive tumours on exemestane. Our study not only showed an impressive reduction in breast cancers, but also an excellent side effect profile, although my cautionary note is that average follow-up to date has been only 3 years."

Oestrogens have been implicated in causing breast cancer. The anti-oestrogens tamoxifen and raloxifene are FDA approved preventatives of breast cancer in women at high risk. However, it has been estimated that rare but serious uterine cancer and blood clots which can be fatal, have limited the acceptance of tamoxifen to only 4 percent of high risk women and 0.08 percent of all women in the U.S. There is a need for highly effective and safer options for breast cancer prevention.

The MAP.3 (Mammary Prevention Trial-.3) study, led and coordinated by the NCIC CTG, is the first randomized trial to assess an aromatase inhibitor as a breast cancer preventative in healthy women. Exemestane is an AI approved by the U.S. Food and Drug Administration for use in early breast cancer patients. The trial enrolled 4,560 women from the U.S., Canada, Spain and France. Eligible postmenopausal women had at least one of these risk factors: age greater than or equal to 60 years; five-year Gail risk score greater than 1.66 percent; prior atypical ductal or lobular hyperplasia or lobular carcinoma in situ; or ductal carcinoma in situ with prior mastectomy.

At a median follow up of three years, the group receiving Exemestane had a 65 percent reduction in invasive cancers (11 invasive breast cancers in the Exemestane group compared to 32 in the placebo group). There was also a 60 percent reduction of invasive breast cancer plus pre-invasive DCIS among the 66 cases in the women on the trial. Importantly, there were fewer cases of cancer precursor lesions such as atypical ductal and atypical lobular hyperplasia in the group receiving Exemestane.

Reference: Abstract: LBA504 ASCO 2011: NCIC CTG MAP.3: A phase III placebo-controlled Breast Cancer Prevention Trial of exemestane in postmenopausal women at risk for breast cancer. P. E. Goss, J. N. Ingle, J. Ales-Martinez, A. Cheung, R. T. Chlebowski, J. Wactawski-Wende, A. McTiernan, J. Robbins, K. Johnson, L. Martin, E. Winquist, G. Sarto, J. E. Garber, C. J. Fabian, P. Pujol, E. Maunsell, P. Farmer, K. A. Gelmon, D. Tu, H. Richardson.