A Comprehensive Analysis of Adverse Events Associated with HER2 Inhibitors Approved for Breast Cancer Using the FDA Adverse Event Report System (FAERS)

Background: /Objectives: Human epidermal growth factor receptor 2 (HER2) inhibitors have significantly improved the prognosis of patients with HER2-positive breast cancer. Currently, HER2 inhibitors, including tyrosine kinase inhibitors targeting HER2 and other HER family members, as well as antibody–drug conjugates, have been developed and are in clinical use. Each of these agents has distinct mechanisms of action and adverse event profiles. In treatment models such as therapy for HER2-positive breast cancer, in which multiple agents with HER2-inhibitory activity are used sequentially or in combination, a comprehensive understanding of the adverse events associated with each drug is beneficial. However, investigations into overall adverse event trends remain limited. Therefore, this study aimed to conduct a comprehensive analysis of the characteristic adverse events associated with HER2 inhibitors. Methods: Using the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database, we performed cluster analysis and principal component analysis (PCA) based on the reporting odds ratios of key adverse events associated with HER2 inhibitors approved for breast cancer treatment. Results: Cluster analysis revealed a strong correlation between monoclonal antibody drugs and hair-related adverse events. PCA indicated that the first component reflects the adverse event occurrence risk, the second differentiates between monoclonal antibodies and tyrosine kinase inhibitors, and the third may serve as an indicator distinguishing molecular targeted agents from antibody–drug conjugates. Conclusions: Analysis of FAERS data enabled comprehensive visualization of the real-world adverse event profiles of individual HER2 inhibitors. These findings are expected to enhance our understanding of safety profiles, support informed drug selection, and contribute to the development of improved adverse event management strategies.