Aromatase inhibitors and the incidence of Parkinson disease: A population-based cohort study

Background Current guidelines recommend the treatment of hormone receptor-positive breast cancer with aromatase inhibitors (AIs) and tamoxifen in the adjuvant setting. Some observational studies have raised concerns that tamoxifen may be associated with an increased risk of Parkinson disease (PD). However, no studies have directly compared the risk of PD between AIs and tamoxifen in women diagnosed with breast cancer. Methods Using the UK Clinical Practice Research Datalink, the authors assembled a cohort of women newly diagnosed with breast cancer and newly treated with either AIs or tamoxifen between January 1, 1995, and December 31, 2017. Patients were followed 1 year after treatment initiation (ie, a 1-year lag) until an incident diagnosis of PD or were censored at death from any cause, the date of transfer out of the practice, or the end of the study period (December 31, 2018). Cox proportional hazards models with inverse probability of treatment weights were used to estimate weighted hazard ratios (HRs) and 95% confidence intervals (CIs) for PD comparing AIs with tamoxifen and accounting for more than 30 confounders. Results In all, 30,140 women with nonmetastatic breast cancer were identified: 13,838 initiated AIs, and 16,302 initiated tamoxifen. Compared with tamoxifen, AIs were not associated with an increased risk of PD (HR, 0.94; 95% CI, 0.60-1.47). Consistent results were observed across all secondary and sensitivity analyses. Conclusions In this large observational study, the use of AIs, in comparison with tamoxifen, was not associated with an increased risk of PD in women diagnosed with nonmetastatic breast cancer in a real-world setting. Lay Summary Previous studies have indicated that tamoxifen may increase the risk of Parkinson disease in the treatment of breast cancer. However, no studies have directly compared the risk of Parkinson disease between aromatase inhibitors and tamoxifen. This study included 30,140 women diagnosed with breast cancer and treated with aromatase inhibitors or tamoxifen. Overall, compared with tamoxifen, aromatase inhibitors were not associated with an increased risk of Parkinson disease in women diagnosed with breast cancer. This study provides an important addition to the comparative safety profile of aromatase inhibitors and tamoxifen in the treatment of breast cancer.