Antibody-drug conjugates in breast cancer: From therapeutic and immune activation mechanisms to resistance prevention

and triple negative breast cancers). These ADCs exert anti-tumor activity through cytotoxic effects and immune responses primarily by recruiting and activating cytotoxic T cells. Moreover, combining ADCs with immune checkpoint inhibitors (ICIs) shows enhanced therapeutic outcomes. ADCs resistance is caused by heterogeneous target antigens expression, modified ADC processing including endocytosis and lysosomal trafficking, as well as upregulated drug-efflux pumps that decrease payload concentration intracellularly. Strategies to mitigate ADCs resistance include multi-target ADCs, and stability-enhancing linkers that also reduce off-target toxicities. ADCs continue to play key roles in breast cancer treatment, while next-generation ADCs may address current ADCs' limitations and resistance mechanisms.