The therapeutic landscape for patients with HER2-positive breast cancer has dramatically changed in recent years. Wolfgang Janni, MD, PhD, University of Ulm, Ulm, Germany, contexualises the results of the DESTINY-Breast03 study demonstrating the superiority of trastuzumab deruxtecan (T-DXd) in HER2-positive breast cancer alongside the findings from the HER2CLIMB study evaluating tucatinib in patients with HER2-positive breast cancer. This interview took place at the European Society for Medical Oncology (ESMO) 2021 congress.