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

Background: The increasingly consistent association between estrogen replac ement therapy and colorectal cancer suggests that the anti-estrogen tamoxif en 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 geograp hically defined, population based cancer registries representing approximat ely ten percent of the U.S. population. Of 85,411 women with local or regio nal breast cancer diagnosed from 1983-90, 14,984 women were reported to hav e received hormonal therapy and 70,427 were not known to have received horm onal therapy. Subsequent cancer diagnoses were identified in this cohort be ginning 6 months after initial breast cancer diagnosis until death, or Dece mber 31, 1994. Multivariate Cox proportional hazards models were used to es timate the risk of developing colorectal cancer and other second cancers ac cording to hormonal therapy use. Results: Over the follow-up period 793 colorectal, 2,648 contralateral brea st, 506 endometrial, 250 ovarian, 98 gastric, and 1,765 other cancers were identified in the study cohort. While overall there was no association betw een 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 aft er diagnosis, risk was increased significantly by about 50% (95% CI 1.00-2. 15). As expected, based upon clinical trials data, cancers of the contralat eral breast were significantly decreased, and cancers of the uterine endome trium were significantly increased. No other meaningful associations were o bserved. When women were excluded for whom hormonal therapy might represent therapy other than tamoxifen (premenopausal women and those who received c hemotherapy), this did not meaningfully alter these estimates. Conclusions: The results of this large population based cohort study sugges t that tamoxifen therapy may modestly increase risk of large bowel cancer i n women, but only after 5 years following initiation of breast cancer thera py.