Menopausal Hormone Therapy and Breast Cancer Risk in the NIH-AARP Diet and Health Study Cohort
- Louise A. Brinton1,
- Douglas Richesson1,
- Michael F. Leitzmann2,
- Gretchen L. Gierach1,
- Arthur Schatzkin2,
- Traci Mouw2,
- Albert R. Hollenbeck3 and
- James V. Lacey, Jr.1
- 1Hormonal and Reproductive Epidemiology Branch, 2Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute; and 3Organizational and Tracking Research Department, AARP, Washington, District of Columbia
- Requests for reprints:
Louise A. Brinton, 6120 Executive Boulevard, Suite 550, Room 5018, Rockville, MD 20852-7234. Phone: 301-496-1693; Fax: 301-402-0916. E-mail: brinton{at}nih.gov
Abstract
Background: Results from the Women's Health Initiative trial raise new questions regarding the effects of estrogen therapy (ET) and estrogen plus progestin therapy (EPT) on breast cancer risk.
Methods: We analyzed data from 126,638 females, ages 50 to 71 years at baseline, who completed two questionnaires (1995-1996 and 1996-1997) as part of the NIH-AARP Diet and Health Cohort Study and in whom 3,657 incident breast cancers were identified through June 30, 2002. Hormone-associated relative risks (RR) and 95% confidence intervals (CI) of breast cancer were estimated via multivariable regression models.
Results: Among thin women (body mass index <25 kg/m2), ET use was associated with a significant 60% excess risk after 10 years of use. EPT was associated with a significantly increased risk among women with intact uteri, with the highest risk among current, long-term (≥10 years) users (RR, 2.44; 95% CI, 2.13-2.79). These risks were slightly higher when progestins were prescribed continuously than sequentially (<15 days/mo; respective RRs of 2.76 versus 2.01). EPT associations were strongest in thin women, but elevated risks persisted among heavy women. EPT use was strongly related to estrogen receptor (ER)-positive tumors, requiring consideration of this variable when assessing relationships according to other clinical features. For instance, ER- ductal tumors were unaffected by EPT use, but all histologic subgroups of ER+ tumors were increased, especially low-grade and mixed ductal-lobular tumors.
Conclusions: Both ET and EPT were associated with breast cancer risks with the magnitude of increase varying according to body mass and clinical characteristics of the tumors. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3150–60)
Footnotes
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Grant support: Intramural Research Program of the NIH, National Cancer Institute. Cancer incidence data were collected for the Atlanta metropolitan area by the Georgia Center for Cancer Statistics, Department of Epidemiology, Rollins School of Public Health, Emory University; for California by the California Department of Health Services, Cancer Surveillance Section; for the Detroit metropolitan area by the Michigan Cancer Surveillance Program, Community Health Administration, State of Michigan; for Florida by the Florida Cancer Data System under contract to the Department of Health; for Louisiana by the Louisiana Tumor Registry, Louisiana State University Medical Center, New Orleans; for New Jersey by the New Jersey State Cancer Registry, Cancer Epidemiology Services, New Jersey State Department of Health and Senior Services; for North Carolina by the North Carolina Central Cancer Registry; and for Pennsylvania by the Division of Health Statistics and Research, Pennsylvania Department of Health, Harrisburg, PA.
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Note: The first author of this article had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
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- Accepted August 26, 2008.
- Received May 13, 2008.
- Revision received July 31, 2008.
