Exemestane for Breast-Cancer Prevention in Postmenopausal Women
Open accessAbstract
BACKGROUND: Tamoxifen and raloxifene have limited patient acceptance for primary prevention of breast cancer. Aromatase inhibitors prevent more contralateral breast cancers and cause fewer side effects than tamoxifen in patients with early-stage breast cancer. METHODS: In a randomized, placebo-controlled, double-blind trial of exemestane designed to detect a 65% relative reduction in invasive breast cancer, eligible postmenopausal women 35 years of age or older had at least one of the following risk factors: 60 years of age or older; Gail 5-year risk score greater than 1.66% (chances in 100 of invasive breast cancer developing within 5 years); prior atypical ductal or lobular hyperplasia or lobular carcinoma in situ; or ductal carcinoma in situ with mastectomy. Toxic effects and health-related and menopause-specific qualities of life were measured. RESULTS: A total of 4560 women for whom the median age was 62.5 years and the median Gail risk score was 2.3% were randomly assigned to either exemestane or placebo. At a median follow-up of 35 months, 11 invasive breast cancers were detected in those given exemestane and in 32 of those given placebo, with a 65% relative reduction in the annual incidence of invasive breast cancer (0.19% vs. 0.55%; hazard ratio, 0.35; 95% confidence interval [CI], 0.18 to 0.70; P=0.002). The annual incidence of invasive plus noninvasive (ductal carcinoma in situ) breast cancers was 0.35% on exemestane and 0.77% on placebo (hazard ratio, 0.47; 95% CI, 0.27 to 0.79; P=0.004). Adverse events occurred in 88% of the exemestane group and 85% of the placebo group (P=0.003), with no significant differences between the two groups in terms of skeletal fractures, cardiovascular events, other cancers, or treatment-related deaths. Minimal quality-of-life differences were observed. CONCLUSIONS: Exemestane significantly reduced invasive breast cancers in postmenopausal women who were at moderately increased risk for breast cancer. During a median follow-up period of 3 years, exemestane was associated with no serious toxic effects and only minimal changes in health-related quality of life. (Funded by Pfizer and others; NCIC CTG MAP.3 ClinicalTrials.gov number, NCT00083174.).
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Both AI trials demonstrated a reduction in risk of ER-positive invasive breast cancer, but no significant effect on ER-negative disease.
“Notably, both trials demonstrated a reduction in the risk of estrogen receptor (ER)-positive invasive breast cancer, but no significant effect on ER-negative disease.”
From Screening, Risk Reduction Strategies, and Clinical Management of Unaffected Carriers of <i>BRCA1</i> or <i>BRCA2</i> Pathogenic Variants (2026) · cites this paper as [67]
Table 2 (Results) supports this pattern for the exemestane trial: ER-positive invasive cancers were significantly reduced (hazard ratio 0.27; P<0.001), while the ER-negative result was not significant (P=0.74). This paper's reported results do not establish the same pattern for the other trial in the claim's “both trials.” (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn the MAP.3 trial, exemestane use was associated with significant reduction in invasive breast cancers in all study subgroups (HR 0.35, 95% CI 0.18-0.70).
“At a median follow-up of almost 3 years, exemestane use was associated with significant reduction in invasive breast cancers in all study subgroups (HR: 0.35, 95% CI: 0.18 - 0.70) [67, 68].”
From Screening, Risk Reduction Strategies, and Clinical Management of Unaffected Carriers of <i>BRCA1</i> or <i>BRCA2</i> Pathogenic Variants (2026) · cites this paper as [67]
The Results report a significant overall reduction in invasive breast cancer at a median follow-up of 35 months (HR 0.35, 95% CI 0.18–0.70). They say exemestane appeared superior in the prespecified subgroups, but do not establish a significant reduction in all subgroups: the reported confidence intervals for prior hormone-therapy nonusers and European participants include 1. (LLM, conf=0.90)
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- Authors
- Goss, P. E., Ingle, J. N., Alés-Martínez, J. E., Cheung, A. M., Chlebowski, R. T., Wactawski-Wende, J., McTiernan, A., Robbins, J., Johnson, K. C., Martin, L. W., Winquist, E., Sarto, G. E., Garber, J. E., Fabian, C. J., Pujol, P., Maunsell, E., Farmer, P., Gelmon, K. A., Tu, D., & Richardson, H.
- Affiliations
- Massachusetts General Hospital (US)
- Mayo Clinic (US)
- University Health Network (CA)
- The Lundquist Institute (US)
- Fred Hutch Cancer Center (US)
- University of California, Davis (US)
- University of Tennessee Health Science Center (US)
- George Washington University (US)
- London Health Sciences Centre (CA)
- University of Wisconsin–Madison (US)
- Dana-Farber Cancer Institute (US)
- University of Kansas Medical Center (US)
- Hôpital Arnaud de Villeneuve (FR)
- Université Laval (CA)
- Queen's University (CA)
- BC Cancer Agency (CA)
- Canadian Cancer Trials Group (CA)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2011-06-23
- Volume
- 364
- Issue
- 25
- Pages
- 2381-2391
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2139434007
- Cited by
- 970
- References
- 4
- Citations by year
- 2026: 21 · 2025: 39 · 2024: 39 · 2023: 47 · 2022: 53 · 2021: 54 · 2020: 51 · 2019: 56 · 2018: 51 · 2017: 75 · 2016: 81 · 2015: 92 · 2014: 85 · 2013: 90 · 2012: 97
- FWCI
- 61.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- RECERCAT (Consorci de Serveis Universitaris de Catalunya) (publishedVersion)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, public-domain)
- Funders
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Keywords
- exemestane, breast cancer prevention, aromatase inhibitors, postmenopausal women, primary prevention, invasive breast cancer, ductal carcinoma in situ, atypical hyperplasia, lobular carcinoma in situ, adverse events, quality of life, menopause, tamoxifen, raloxifene, fracture risk, cardiovascular events, non-relapse mortality
- MeSH terms
- Adult, Aged, Aged, 80 and over, Androstadienes, Breast Neoplasms, Carcinoma, Intraductal, Noninfiltrating, Double-Blind Method, Female, Follow-Up Studies, Humans, Middle Aged, Neoplasm Invasiveness, Quality of Life, Risk Factors, Incidence, Postmenopause, Aromatase Inhibitors
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