Cardiovascular Safety of Next-Generation Antibody-Drug Conjugates in HER2-Low and Triple-Negative Breast Cancer: A Narrative Review (2020-2025)

The clinical validation of the HER2-low phenotype has expanded eligibility for HER2-targeted antibody-drug conjugates (ADCs). Trastuzumab deruxtecan (T-DXd) introduces a novel cardiotoxicity profile driven by both HER2 inhibition and payload-mediated off-target injury. A narrative review of recent literature and pharmacovigilance reports identifies a notable incidence of left ventricular ejection fraction (LVEF) decline with T-DXd, which is disproportionately higher than that of earlier-generation ADCs. In contrast, TROP2-directed ADCs demonstrate negligible cardiac signals. Given the elevated fatality rate of serious cardiac events associated with T-DXd observed in real-world data, we propose a risk-stratified cardiac monitoring algorithm incorporating high-sensitivity troponin and global longitudinal strain for patients receiving next-generation ADCs.