Abstract
Antibody-drug conjugates (ADCs) have revolutionized the treatment landscape for metastatic breast cancer, offering targeted delivery of cytotoxic agents with improved efficacy and tolerability compared to conventional chemotherapy. This narrative review explores key predictive factors influencing the efficacy of ADCs, focusing on HER2-targeted therapies, such as trastuzumab emtansine and trastuzumab deruxtecan, as well as sacituzumab govitecan for triple-negative breast cancer. HER2 expression, TROP-2 levels, hormone receptor status, and the tumor microenvironment emerge as critical biomarkers for patient selection and therapeutic outcomes. Additionally, we discuss resistance mechanisms, such as antigen loss, impaired drug internalization, and the role of circulating tumor DNA in predicting ADC response. Finally, future perspectives on the sequential use of ADCs and potential combination therapies are highlighted, along with emerging agents targeting alternative antigens like HER3 and LIV-1. Overall, identifying predictive biomarkers and overcoming resistance mechanisms are essential for optimizing the use of ADCs in metastatic breast cancer, thereby improving patient outcomes.