Abstract
BACKGROUND: Some antineoplastic agents have been implicated in cardiac failure (CF), but large-scale real-world data remain limited. This study aimed to assess disproportional reporting signals for CF associated with novel antineoplastic agents used in breast cancer treatment. METHODS: A disproportionality analysis was conducted using individual case safety reports from the FDA Adverse Event Reporting System (FAERS, Jan 2004-Mar 2025), Canada Vigilance Adverse Reaction Database (CANADA, Jan 2004-Dec 2024), and Japanese Adverse Drug Event Report (JADER, Jan 2004-Oct 2024). Reports involving breast cancer patients treated with FDA-approved targeted agents were included. Reporting odds ratios (RORs), time-to-onset (TTO), and death proportion were evaluated by drug and class. RESULTS: A total of 8,565 CF cases were identified across the three databases. Trastuzumab exhibited consistently strong signals (FAERS: ROR 2.94; CANADA: 6.15; JADER: 7.05), with pertuzumab and everolimus showing variable significance. CDK4/6 inhibitors and immune checkpoint inhibitors (ICIs) demonstrated low or inverse RORs. Median TTO was longest for monoclonal antibodies, and shorter for ADCs and ICIs. Everolimus (20.1%), sacituzumab govitecan (22.6%), and atezolizumab (23.5%) showed the highest death proportions, while trastuzumab had a lower proportion (8.75%). HER2-targeted agents had higher reporting signal of CF than traditional chemotherapies. CONCLUSION: This study underscores drug-specific differences in CF risk among breast cancer therapies and highlights the importance of individualized cardiovascular risk assessment during treatment planning and monitoring.