Antibody-drug conjugates in breast cancer: from mechanism to revolutionizing clinical practice

The advent of antibody-drug conjugates (ADCs) has caused a paradigm shift in breast cancer management, transforming the treatment landscape from advanced lines to curative-intent settings. By integrating the specificity of monoclonal antibodies with the potency of cytotoxic payloads, ADCs have broken the limitations of traditional chemotherapy. This review aims to provide a comprehensive overview of the current state of ADCs in breast cancer, concentrating on targets under development, toxicity, and the challenges that remain to be overcome. Distinct from conventional classifications, we propose a framework categorizing ADC targets into three dimensions based on biological features: oncogenic driver antigens, lineage and oncofetal antigens, and tumor microenvironment antigens. Meanwhile, we discuss the structural evolution of ADCs, the management of toxicity, and the mechanism-based resistance. The future of treatment calls for precise ADC management, the use of next-generation bispecific ADCs and immune-oncology combinations, and the imperative of biomarker-guided sequencing.