Therapeutic Advances in Medical Oncology (Mar 2020)
Thromboembolic, cardiovascular and overall mortality risks of aromatase inhibitors, compared with tamoxifen treatment: an outpatient-register-based retrospective cohort study
Abstract
Background: Tamoxifen (TAM) and aromatase inhibitor (AI) therapies have been associated with increased risk of thromboembolic and cardiovascular events, respectively, in addition to other side effects. This study analysed the risk of these events and the overall survival (OS) benefit in breast cancer patients treated with AI, compared with TAM-treated patients, in a large population-based cohort. Methods: This observational cohort study included women diagnosed with breast cancer and treated with TAM or AI. Data were extracted from primary care records in a population database (SIDIAP, System for the Development of Research in Primary Care). Incidence rates of study outcomes are reported. Survival analyses included Kaplan–Meier estimation and Cox proportional hazards models. Sensitivity analysis was carried out, using Fine and Gray models to account for competing risk of death. Confounding was minimized using propensity score adjustment and inverse probability weighting (IPW) adjustment. Results: Data from 3082 postmenopausal women treated with TAM, and 18,455 treated with AI, were available. Adjusted hazard ratios (HRs) [95% confidence interval (CI)] for AI users, compared with TAM group, were 0.93 (95%CI 0.69–1.26) for thromboembolic events (TEEs); 1.13 (95%CI 0.79–1.63) for cardiovascular events, and 0.76 (95%CI 0.70–0.82) for mortality. Additional analyses using competing risk analysis had similar results, while IPW adjustment showed a potential risk of pulmonary embolism (PE) [2.26 (95%CI 1.02–4.97)] in AI-treated patients. Conclusions: AI users had >20% lower all-cause mortality compared with TAM users, without increasing risk to experience cardiovascular and TEEs. This would locate AI therapy on the first line in clinical practice. Thus, AI might be the most preferable option in adjuvant hormonal therapy choice.