Recent results presented at SABCS 2025 highlight the expanding role of trastuzumab deruxtecan (T-DXd) in HER2-positive early breast cancer. Findings from DESTINY-Breast05 demonstrated improved invasive disease–free survival with adjuvant T-DXd compared with T-DM1 in patients with residual high-risk disease after neoadjuvant therapy. The DESTINY-Breast11 trial also explored T-DXd in the neoadjuvant setting, showing higher pathologic complete response rates in select high-risk populations. Drs. Reshma Mahtani, Heather McArthur, and Anne O’Dea discuss how these results may influence treatment sequencing, with many clinicians currently reserving T-DXd for adjuvant therapy in patients with residual disease.