Reconciling Trial Design, FDA Labels, and NCCN Guidance in HER2-Positive Early Breast Cancer

This OncLive News Network program explores evolving treatment strategies for patients with HER2-positive early breast cancer, with a focus on translating emerging clinical trial evidence into clinical practice. Dr. Ruta Rao and Dr. Jason Mouabbi discuss the current treatment continuum from neoadjuvant therapy through surgery and post-neoadjuvant treatment, including the role of pathologic response in guiding subsequent management. They review findings from the DESTINY-Breast11 trial and consider how its high-risk study population relates to the broader FDA-approved neoadjuvant indication and current NCCN recommendations. The discussion then moves to the post-neoadjuvant setting, comparing the high-risk population and findings from DESTINY-Breast05 with the established evidence from KATHERINE, including considerations for T-DXd and T-DM1 selection. Dr. Rao and Dr. Mouabbi also discuss treatment sequencing, individual patient selection, and practical considerations surrounding T-DXd-associated interstitial lung disease, emphasizing the importance of monitoring and multidisciplinary coordination when treating HER2-positive early breast cancer.