Cardiotoxicity with human epidermal growth factor receptor-2 inhibitors in breast cancer: Disproportionality analysis of the FDA adverse event reporting system

The cardiotoxicity induced by human epidermal growth factor receptor-2 (HER-2) inhibitors in patients with breast cancer has been reported widely. However, these data sources were largely limited to fewer patients in clinical trials and case reports, lacking more comprehensive analysis from real-world data.The cases diagnosed with breast cancer from January 2004 to December 2021 were extracted from the FDA adverse event database and further divided into 3 groups (the HER-2 inhibitor group, the positive control group, and the control group). The association between HER-2 inhibitors and cardiovascular adverse events was evaluated using the reporting odds ratio (ROR), a disproportionality method.A total of 167,639 breast cancer patients were included, including 18,615 cases in the HER-2 inhibitor drug group, 2568 cases in the positive control group, and 146,456 cases in the control group. A total of 2529 cases (13.5%) treated with HER-2 inhibitors experienced cardiovascular adverse events, mainly reported by health professionals (81.5%). The disproportionality analysis showed that cardiomyopathy was observed in all HER-2 inhibitors except trastuzumab deruxtecan. Trastuzumab-related CVAEs were most frequently reported (N =2075), and the median time was 80.50 days (IQR: 8.00 to 206.75 days).Based on real-world data analysis, our study demonstrated a significant association between HER-2 inhibitors and cardiovascular toxicity. Cardiac function in patients with breast cancer should be monitored early during anti-HER therapy, especially within six months.