Abstract
PURPOSE: Among a cohort of postmenopausal breast cancer survivors, we aimed to compare the risk of dementia associated with aromatase inhibitor (AI) therapy versus tamoxifen. METHODS: Using UK primary care electronic health records, we identified 14,214 postmenopausal breast cancer survivors (aged ≥ 54 years) with a first AI or tamoxifen prescription between January 2002 and December 2015 and no previous dementia diagnosis. Women were followed-up to identify incident cases of dementia. Cox regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) to quantify the association between AI exposure (vs. tamoxifen) and dementia, adjusted for confounders. RESULTS: A total of 368 incident dementia cases was identified over 57,102 person-years of follow-up. The crude incidence rate of dementia was 7.46 per 1000 person-years (95% CI 6.43-8.65) among women starting endocrine treatment on an AI, and 6.32 per 1000 person-years (95% CI 5.34-7.47) among women starting on tamoxifen. After accounting for age differences and assessing other potential confounders, there was no evidence of a difference in dementia risk between exposure groups (HR for AI vs tamoxifen 1.04, 95% CI 0.83-1.03). There was no evidence of effect modification by age. CONCLUSION: There was no evidence for a difference in dementia risk between AI and tamoxifen users among postmenopausal breast cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Our findings suggest that there is no reason for concern about a difference in dementia risk with AI vs. tamoxifen, which is relevant to postmenopausal breast cancer patients recommended these treatments.