© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 19, 1654-1662,
October 6, 1999
© 1999 Oxford University Press
Tamoxifen Therapy for Breast Cancer and Endometrial Cancer Risk
Affiliations of authors: L. Bernstein, D. Deapen, E. McGann-Maloney, Department of Preventive Medicine, University of Southern California School of Medicine, and Norris Comprehensive Cancer Center, Los Angeles; J. R. Cerhan, Department of Health Sciences Research, Mayo Clinic, Rochester, MN; S. M. Schwartz, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, and Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle; J. Liff, Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA; J. A. Perlman, U.S. Public Health Service and Epimedix, Washington, DC; L. Ford, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD.
Correspondence to: Leslie Bernstein, Ph.D., Department of Preventive Medicine, University of Southern California/Norris Comprehensive Cancer Center, 1441 Eastlake Ave., MS 44, Los Angeles, CA 90033 (e-mail: lbern{at}hsc.usc.edu).
BACKGROUND: Tamoxifen is effective in treating breast cancer, reduces breast cancer incidence among high-risk women, and is associated with increased endometrial cancer risk. This study was designed to examine the possible modifying effects of endometrial cancer risk factors on the tamoxifen-endometrial cancer association. METHODS: We conducted a case-control study of endometrial cancer (324 case patients and 671 individually matched control subjects) nested within a population-based cohort of patients with breast cancer diagnosed from 1978 through 1992 within four regions of the United States. We obtained information on breast cancer treatment and endometrial cancer risk factors through interviews and reviews of medical records. All P values reported are two-sided. RESULTS: Endometrial cancer risk was associated with tamoxifen therapy for breast cancer (odds ratio = 1.52; 95% confidence interval [CI] = 1.07-2.17). Risk increased with duration of tamoxifen use (P for trend = .0002). Women with more than 5 years of exposure to tamoxifen had 4.06-fold greater odds of developing endometrial cancer than nonusers (95% CI = 1.74-9.47). Prior use of estrogen replacement therapy (ERT) increased risk associated with tamoxifen use (P for homogeneity of trends <.0001). Risk associated with tamoxifen use was stronger among heavier women than among thinner women, although trends did not differ statistically (P = .10). Tamoxifen dose-response effects were more pronounced among women with both previous ERT exposure and higher body mass index than among women in other risk groups. CONCLUSIONS: ERT use and obesity, both established endometrial cancer risk factors and markers of estrogen exposure, substantially modify the association between tamoxifen use and endometrial cancer risk among patients with breast cancer. Women with positive ERT histories and those who are obese, when prescribed tamoxifen, may warrant closer surveillance for endometrial cancer than women without such histories.
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