The development of antibody-drug conjugates composed of a cytotoxic agent and a 
monoclonal antibody carrier offers an important alternative to classic 
chemotherapy strategies. Trastuzumab deruxtecan (DS-8201a) is a next-generation 
antibody-drug conjugate composed of a monoclonal anti-HER2 antibody and a 
topoisomerase I inhibitor, an exatecan derivative (DX-8951f). DS-8201a resulted 
in favorable outcomes in HER2-positive heavily pretreated breast cancer patients 
and also had a promising efficacy in patients with HER2-negative/low-expressing 
disease, whose options are limited. Interestingly, a recently published phase 2 
trial (NCT03248492) reported 60% overall response and 97% disease control in 
patients with HER2-positive disease previously treated with multiple regimens, 
including trastuzumab emtansine. On the basis of recent clinical trials, the US 
Food and Drug Administration granted accelerated approval to DS-8201a in 
advanced or unresectable HER2-positive breast cancer pretreated with at least 
two HER2-targeting treatment lines. We review all preclinical and clinical data 
of DS-8201a regarding breast cancer.