Tamoxifen and risk of large bowel cancer in women with breast cancer

Background: The increasingly consistent association between estrogen replacement therapy and colorectal cancer suggests that the anti-estrogen tamoxifen may also be associated with large bowel cancer incidence.Methods: Women with new diagnoses of breast cancer were identified from the Surveillance Epidemiology and End Results (SEER) Program, a set of geographically defined, population based cancer registries representing approximately ten percent of the U.S. population. Of 85,411 women with local or regional breast cancer diagnosed from 1983–90, 14,984 women were reported to have received hormonal therapy and 70,427 were not known to have received hormonal therapy. Subsequent cancer diagnoses were identified in this cohort beginning 6 months after initial breast cancer diagnosis until death, or December 31, 1994. Multivariate Cox proportional hazards models were used to estimate the risk of developing colorectal cancer and other second cancers according to hormonal therapy use.Results: Over the follow-up period 793 colorectal, 2,648 contralateral breast, 506 endometrial, 250 ovarian, 98 gastric, and 1,765 other cancers were identified in the study cohort. While overall there was no association between hormonal therapy use and colorectal cancer (relative risk (RR) 1.09, 95% confidence interval (CI) 0.88–1.35), in the period five or more years after diagnosis, risk was increased significantly by about 50% (95% CI 1.00–2.15). As expected, based upon clinical trials data, cancers of the contralateral breast were significantly decreased, and cancers of the uterine endometrium were significantly increased. No other meaningful associations were observed. When women were excluded for whom hormonal therapy might represent therapy other than tamoxifen (premenopausal women and those who received chemotherapy), this did not meaningfully alter these estimates.Conclusions: The results of this large population based cohort study suggest that tamoxifen therapy may modestly increase risk of large bowel cancer in women, but only after 5 years following initiation of breast cancer therapy.