Tamoxifen treatment for breast cancer and risk of endometrial cancer: a case-control study.
BACKGROUND
Tamoxifen treatment of breast cancer is associated with an increased risk of endometrial cancer, but tamoxifen-related risks of endometrial cancer are unclear in premenopausal women, in long-term users of tamoxifen, and in women for whom several years have passed since ending treatment. We conducted a case-control study in Britain to investigate these risks.


METHODS
We compared treatment information on 813 case patients who had endometrial cancer after their diagnosis for breast cancer and 1067 control patients who had breast cancer but not subsequent endometrial cancer. We assessed risk by conditional logistic regression analysis. All statistical tests were two-sided.


RESULTS
Overall, tamoxifen treatment, compared with no treatment, was associated with an increased risk of endometrial cancer (odds ratio [OR] = 2.4; 95% confidence interval [CI] = 1.8 to 3.0). Risk increased statistically significantly (P(trend)<.001) with duration of treatment (for > or =5 years of treatment compared with no treatment, OR = 3.6, 95% CI = 2.6 to 4.8). As an indication of background levels of treatment, 16% of control patients received 5 years or more of treatment. Risk of endometrial cancer adjusted for treatment duration did not diminish in follow-up to at least 5 years after the last treatment ended. Risk of endometrial cancer was not associated with the daily dose of tamoxifen and was comparable in pre- and postmenopausal women. Ever treatment with tamoxifen was associated with a much greater risk of Mullerian and mesodermal mixed endometrial tumors (OR = 13.5, 95% CI = 4.1 to 44.5) than of adenocarcinoma (OR = 2.1, 95% CI = 1.6 to 2.7) or clear cell and papillary serous tumors (OR = 3.1, 95% CI = 0.8 to 17.9).


CONCLUSIONS
There is an increasing risk of endometrial cancer associated with longer tamoxifen treatment, extending well beyond 5 years. The increased risk of endometrial cancer associated with tamoxifen treatment should be considered clinically for both premenopausal and postmenopausal women during treatment and for at least 5 years after the last treatment.
Swerdlow
Anthony J
AJ
Section of Epidemiology, Brookes Lawley Building, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK. anthony.swerdlow@icr.ac.uk
Jones
Michael E
ME
D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000517:prevention & control*; D016022:Case-Control Studies; D016889:Endometrial Neoplasms / Q000139:chemically induced*; D004739:England; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D018199:Mixed Tumor, Mesodermal / Q000139:chemically induced; D018200:Mixed Tumor, Mullerian / Q000139:chemically induced; D016017:Odds Ratio; D018570:Risk Assessment; D012307:Risk Factors; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects*; D013997:Time Factors
D018931:Antineoplastic Agents, Hormonal; D020847:Estrogen Receptor Modulators; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen