2011

Exemestane for primary prevention of breast cancer in postmenopausal women: NCIC CTG MAP.3—A randomized, placebo-controlled clinical trial.

Journal of Clinical Oncology, 29 mai 2011; Abstract LBA504

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; Massachusetts General Hospital, Boston, MA ; Mayo Clinic, Rochester, MN ; Hosp Ruber Internacional, Madrid, Spain; Universtiy Health Network, Toronto, ON , Canada; Harbor-UCLA Medical Center, Torrance, CA ; University of Buffalo, Buffalo, NY; Fred Hutchinson Cancer Research Center, Seattle, WA; University of California, Davis, Sacramento, CA ; University of Tennessee  Health Science Center, Memphis, TN ; George Washington University School of Medicine, Washington, DC ; London Health Sciences Centre, London, ON , Canada; Center for Women's Health and Health Research, Madison, WI; Dana-Farber Cancer Institute, Boston, MA ; Kansas University Medical Center, Kansas City, KS ; CHU-Hopital Arnaud de Villeneuve, Montpellier, France; Laval University, Quebec City, QC , Canada; Queen's University Pathology and Molecular Medicine, Kingston, ON , Canada; British Columbia Cancer Agency, Vancouver, BC , Canada; NCIC Clinical Trials Group, Kingston, ON , Canada

 

Background

Limited efficacy and serious toxicities have limited uptake of tamoxifen or raloxifene as preventatives of breast cancer. Aromatase inhibitors (AIs) prevent contralateral breast cancers more than tamoxifen in adjuvant trials and have fewer serious side effects. This is the first report of an AI used in primary prevention.

 

 Methods

 NCIC CTG MAP.3 is a randomized trial designed to detect a 65% reduction in annual incidence of invasive breast cancer (IBC) on exemestane (E) versus placebo (P). Eligible postmenopausal women had ≥ one of the following risk factors: Gail score >1.66%, prior ADH, ALH, LCIS or DCIS with mastectomy, age over 60. Health-related and menopause-specific quality of life (QOL) were assessed by SF-36 and MENQOL questionnaires.

 

Results

From 2004-2010, 4,560 women were randomized: age 62.5 yrs (37-90); Gail Score 2.3 % (0.6-21); BMI 28.0 kg/m2 (15.9-65.4). Risk factors included: age >60 yrs (49%); Gail score >1.66 (40%); and prior ADH, ALH, LCIS or DCIS with mastectomy (11%). At median follow-up of 35 months there were 11 IBCs on E and 32 on P (annual incidence 0.19% vs 0.55%; HR= 0.35, 95% CI 0.18-0.70, p = 0.002); ductal (10E/27P), lobular (1E/5P). Most tumors were ER positive (7E/27P); Her2/neu negative (10E/26P); TNM stage T1 (8E/28P), N0 (7E/22P), M0 (11E/30P). E was superior in all subgroups: by Gail score, age, BMI, prior LCIS and DCIS. The annual incidence rate of IBC or DCIS was 0.35% E and 0.77% P (HR=0.47;95% CI 0.27-0.79; p = 0.004) based on 64 IBCs or DCISs (20E/44P). Clinical bone fractures, osteoporosis, hypercholesterolemia or cardiovascular events were equal in both arms. No clinically meaningful differences in QOL were detected.

 

Conclusions

Exemestane significantly reduced invasive and pre-invasive breast cancers in postmenopausal women at increased risk for breast cancer with no serious toxicities. Exemestane should be considered a new option for primary prevention of breast cancer. Supported by the Canadian Cancer Society; Pfizer Inc. PEG supported in part by Avon Foundation.