Adjuvant Hormonotherapy and Cardiovascular Risk in Post-Menopausal Women with Breast Cancer: A Large Population-Based Cohort Study

SIMPLE SUMMARY: For post-menopausal women with estrogen-receptor-positive breast cancer, treatment with aromatase inhibitors reduces disease recurrence and mortality, as compared to tamoxifen. Nevertheless, women treated with aromatase inhibitors more often develop hyperlipidemia, hypercholesterolemia and hypertension, which are recognized cardiovascular (CV) risk factors. Concerns about CV safety of aromatase inhibitors had been raised by several studies. Our results showed that adjuvant therapy with aromatase inhibitors of breast cancer women is associated with increased risk of heart failure and combined CV events, and such therapy probably amplifies the “intrinsic” CV risk of the patient. They underline the importance of interdisciplinary collaboration between oncologists and cardiologists in evaluating the risk/benefit ratio of the choice of hormone therapy. ABSTRACT: Background: Whether aromatase inhibitors (AIs) increase the risk of cardiovascular (CV) events, compared to tamoxifen, in women with breast cancer is still debated. We evaluated the association between AI and CV outcomes in a large population-based cohort of breast cancer women. Methods: By using healthcare utilization databases of Lombardy (Italy), we identified women ≥50 years, with new diagnosis of breast cancer between 2009 and 2015, who started adjuvant therapy with either AI or tamoxifen. We estimated the association between exposure to AI and CV outcomes (including myocardial infarction, ischemic stroke, heart failure or any CV event) by a Cox proportional hazard model with inverse probability of treatment and censoring weighting. Results: The study cohort included 26,009 women starting treatment with AI and 7937 with tamoxifen. Over a median follow-up of 5.8 years, a positive association was found between AI and heart failure (Hazard Ratio = 1.20, 95% CI: 1.02 to 1.42) and any CV event (1.14, 1.00 to 1.29). The CV risk increased in women with previous CV risk factors, including hypertension, diabetes and dyslipidemia. Conclusions: Adjuvant therapy with AI in breast cancer women aged more than 50 years is associated with increased risk of heart failure and combined CV events.