Background
Trastuzumab deruxtecan (T-DXd) is widely used as a treatment for metastatic HER-2 low and HER2-positive breast cancer, and preclinical studies have suggested multiple potential mechanisms of resistance. There have, however, been few large population-based studies of resistance.
Following the course of trastuzumab deruxtecan through the cancer cell (Fig 1), we combined Next Generation Sequencing (NGS), immunohistochemistry (IHC) and claims data to evaluate clinically relevant mechanisms of resistance to this agent.