Therapies of Breast Cancer by Antibody-Drug Conjugates

Breast cancer remains the most common malignancy in women globally, representing a significant clinical challenge despite recent therapeutic advances. Antibody-drug conjugates (ADCs) represent a paradigm shift in targeted cancer therapy, combining the specificity of monoclonal antibodies with the cytotoxic potency of chemotherapeutic agents. This review examines the current landscape of ADC-based therapies for breast cancer, encompassing mechanistic principles, clinically approved agents, and emerging therapeutic strategies. Trastuzumab deruxtecan (T-DXd/Enhertu) has demonstrated superior efficacy compared to first- generation ADCs in HER2-positive breast cancer, while sacituzumab govitecan (SG/Trodelvy) represents the first Trop-2-directed ADC with clinical efficacy in triple-negative breast cancer. Recent evidence extends ADC applications to HER2-low expressing tumors, expanding treatment populations. Key technical innovations including linker chemistry, payload optimization, and bystander effect mechanisms have enhanced ADC therapeutic indices. Resistance mechanisms and toxicity management remain critical considerations. Future directions include combinations with immunotherapy, exploration of novel targets (Trop-2, B7H3, HER3), development of bispecific ADCs, and personalized approaches based on biomarker assessment. This comprehensive review synthesizes current knowledge on ADC biology, clinical efficacy, safety profiles, and emerging therapeutic opportunities that promise to expand treatment options and improve outcomes for diverse breast cancer populations.