Aromatase Inhibitors, Tamoxifen, and Endometrial Cancer in Breast Cancer Survivors

BackgroundBoth endometrial cancer and postmenopausal breast cancer risk are increased by obesity and higher endogenous estrogen levels. While aromatase inhibitors reduce breast cancer incidence, their influence on endometrial cancer risk is uncertain. Methods We addressed this issue in a cohort of 17,064 women diagnosed with hormone receptor positive breast cancer in an integrated group practice health plan. Information on demographics, comorbidities and adjuvant endocrine therapy use was available from electronic medical and pharmacy records, respectively. Endometrial cancer information was obtained from the health plan’s SEER-affiliated tumor registry and rates were compared across endocrine therapy groups(aromatase inhibitor [n=5,303], tamoxifen [n=5155] , switchers [both n=3787] or none [n=2819]using multi-variable adjusted Cox proportional hazard models. Results Endometrial cancer incidence was a statistically significant, 48% lower in the aromatase inhibitor versus tamoxifen group (HR 0.52, 95% CI 0.31-0.87, P=0.01). Endometrial cancer incidence was 29% lower in the aromatase inhibitor versus no endocrine therapy group (HR 0.71, 95% CI 0.37-1.35, P=0.30) and was 36% higher in the tamoxifen versus no endocrinetherapy group (HR 1.36, 95% CI 0.84-2.22, P=0.22), but neither difference was statisticallysignificant. Associations were stronger among those with good drug adherence. Conclusions In a real world experience, endometrial cancer incidence was lower in women on aromatase inhibitor compared to tamoxifen. Additionally, aromatase inhibitors may mitigate tamoxifen-associated endometrial cancer incidence. While there were somewhat fewer endometrial cancers diagnosed in aromatase inhibitor versus no endocrine therapy users, further studies areneeded for definitive assessment of aromatase inhibitor endometrial cancer influence