Cardiovascular and Metabolic Adverse Events of Endocrine Therapies in Women with Breast Cancer: A Disproportionality Analysis of Reports in the FDA Adverse Event Reporting System

INTRODUCTION: Emerging evidence suggests potential cardiovascular toxicities from oral endocrine therapies (ETs); however, results are conflicting. This study comprehensively examined adverse reactions of ETs and investigated cardiovascular and metabolic safety signals within the FDA Adverse Event Reporting System (FAERS). METHODS: Reports in the FAERS through December 2023 were analyzed for documented reactions to tamoxifen, letrozole, anastrozole, and exemestane in female breast cancer patients. Standardized queries were used to identify cases of cardiovascular (myocardial infarction, heart failure, arrhythmia, stroke) and metabolic (hypertension, dyslipidemia, hyperglycemia) disorders. Descriptive and disproportionality analyses were performed to assess reports and detect safety signals. RESULTS: Among 14,327 unique ET-related reports, arthralgia (n = 1873 events) was the most prevalent reaction. We identified 2170 cardiovascular and 2252 metabolic events associated with ETs. Letrozole had the highest reporting rate of cardiac arrhythmia (7.7%) and showed positive signals for both arrhythmia (reporting odds ratio [ROR] = 2.2; 95% confidence interval [CI]: 1.8-2.5) and myocardial infarction (ROR = 1.9; 95% CI: 1.4-2.6). We also observed a significantly increased risk of heart failure with letrozole (ROR = 1.3; 95% CI: 1.1-1.6) and stroke with tamoxifen (ROR = 1.7; 95% CI: 1.5-2.1). Only anastrozole was significantly associated with metabolic dysfunctions with a notable hyperglycemia reporting rate of 12.2%. CONCLUSION: Our findings provide valuable evidence on common reactions as well as controversial cardiovascular and metabolic abnormalities associated with the real-world use of ETs for breast cancer. Ongoing benefit-risk assessment and close monitoring of cardiac function during treatment, particularly in high-risk women, are warranted to optimize cancer outcomes while minimizing cardiovascular injury.