Tamoxifen therapy for breast cancer and endometrial cancer risk

Background: Tamoxifen is effective in treating breast cancer, reduces breas t cancer incidence among high-risk women, and is associated with increased endometrial cancer risk, This study was designed to examine the possible mo difying effects of endometrial cancer risk factors on the tamoxifen-endomet rial cancer association. Methods: We conducted a case-control study of endo metrial cancer (324 case patients and 671 individually matched control subj ects) nested within a population-based cohort of patients with breast cance r 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 valu es 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) incre ased 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 bot h previous ERT exposure and higher body mass index than among women in othe r risk groups, Conclusions: ERT use and obesity, both established endometri al cancer risk factors and markers of estrogen exposure, substantially modi fy the association between tamoxifen use and endometrial cancer risk among patients with breast cancer. Women with positive ERT histories and those wh o are obese, when prescribed tamoxifen, may warrant closer surveillance for endometrial cancer than women without such histories.