Evaluating seizures associated with novel antineoplastic agents during breast cancer treatment using the Food and Drug Administration Adverse Event Reporting System and Canada Vigilance Adverse Reaction Online Database

Background: There is a rising incidence of neurological adverse events (AEs), such as seizures, associated with novel anticancer agents, warranting investigation. Large-scale studies assessing seizure risk across diverse anticancer drug classes, particularly in breast cancer (BC), remain limited. Objective: This study aimed to systematically evaluate the association between seizures and 14 novel anticancer agents used in BC treatment, compared with traditional chemotherapy, utilizing international pharmacovigilance databases. Design: A large-scale, real-world pharmacovigilance study using data from the US FDA Adverse Event Reporting System (FAERS) and the Canada Vigilance Database (from Q1 2004 to Q1 2025). Methods: Disproportionality analysis was employed to calculate reporting odds ratios (RORs) for identifying significant seizure AE signals. Signals were assessed at both the Standardised MedDRA Query and Preferred Term levels. Pan-cancer transcriptomic data from The Cancer Genome Atlas were integrated to explore biological pathways correlated with drug-induced seizures. Results: Significant and consistent seizure signals were identified for five agents—Lapatinib, Tucatinib, Trastuzumab, Trastuzumab Emtansine (T-DM1), and Atezolizumab—across both databases. In FAERS, over 50% of seizures occurred after 100 days of treatment (median: 68 days); however, fatal cases exhibited a significantly shorter median onset time. Novel agents demonstrated disproportionately higher seizure reporting signals compared to traditional chemotherapy. Pan-cancer analysis revealed negative correlations between seizure RORs and pathways, including asthma and the pentose phosphate pathway. Conclusion: This dual-database pharmacovigilance study identifies potential associations between seizures and five novel BC therapies, underscoring the need for vigilant monitoring during their clinical use.