Background: Prior studies regarding use of Aromatase inhibitors (AIs) and risk for cardiovascular disease (CVD) have shown conflicting results. This retrospective cohort study aimed to investigate whether AIs use affects risk for CVD events in postmenopausal breast cancer survivors. Methods: Using a retrospective cohort study design, four CVD outcomes; heart failure or cardiomyopathy, arrhythmia, acute ischemic heart disease and ischemic stroke or Transient Ischemic Attack were compared with uni-and multivariate Cox regression analyses according to exposure to endocrine therapy (use of AI, tamoxifen or AI/tamoxifen sequentially) or no endocrine therapy. Results: In total 15815 postmenopausal women, surgically treated to early breast cancer during 2006 e2012, were included. No significantly increased risk for CVD events was observed in patients with AI use in the whole cohort. However, two subgroup analyses showed increased risk for CVD events in the AI/tamoxifen sequential group; heart failure in patients older than 75 years (Hazard Ratio (HR) 2.44; 95% Confidence Interval (CI): 1.32e4.54) and arrhythmia in patients without prior CVD (HR 1.45; 95% CI: 1.01 e2.10). An increased risk for arrhythmia and acute ischemic heart disease in patients with at least four years of AI treatment compared with no or short-time exposure was observed (HR 2.12; 95% CI: 1.40 e3.25 for arrhythmia; HR 2.03; 95% CI: 1.15e3.58 for ischemic heart disease). Conclusion:Our results indicate an increased risk for ischemic heart disease and arrhythmia in patients treated for more than four years with AIs. This should be considered in the risk-benefit assessment concerning endocrine therapy.

Purpose The safety of local estrogen therapy in patients on adjuvant endocrine treatment is questioned, but evidence on the issue is scarce. This nested case–control registry-based study aimed to investigate whether estrogen therapy affects breast cancer mortality risk in women on adjuvant endocrine treatment. Methods In a cohort of 15,198 women diagnosed with early hormone receptor (HR)-positive breast cancer and adjuvant endocrine treatment, 1262 women died due to breast cancer and were identified as cases. Each case was matched with 10 controls. Exposure to estrogen therapy with concurrent use of aromatase inhibitors (AIs), tamoxifen, or both sequentially, was compared between cases and controls. Results No statistically significant difference in breast cancer mortality risk was seen in patients with exposure to estrogen therapy concurrent to endocrine treatment, neither in short-term or in long-term estrogen therapy use. Conclusions The study strengthens current evidence on local estrogen therapy use in breast cancer survivors, showing no increased risk for breast cancer mortality in patients on adjuvant AIs or tamoxifen.