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"n a patient with metastatic HER2-positive breast cancer, what should guide the next decision: trial data, toxicity, or durability of response? In this episode of BackTable Tumor Board, Dr. Lindsay Peterson (Washington University) sits down with Dr. Erica Hamilton (Sarah Cannon Research Institute) to examine how next-generation HER2-directed therapies are reshaping the management of metastatic disease. As treatment options expand beyond trastuzumab-based regimens to agents such as trastuzumab deruxtecan and tucatinib, clinical decision-making increasingly hinges on sequencing strategy, interpretation of evolving trial data, and thoughtful toxicity management. --- SYNPOSIS The discussion integrates findings from pivotal studies including DESTINY-Breast09 and PATINA, highlighting how these data influence frontline and maintenance approaches. Dr. Hamilton outlines practical considerations in balancing depth and durability of response with quality-of-life concerns, and how she approaches therapy transitions in real-world practice. The episode also explores the management of CNS involvement within the broader systemic treatment landscape and considers whether current advances meaningfully shift long-term outcomes for patients with HER2-positive metastatic breast cancer. --- TIMESTAMPS 00:00 - Introduction 01:16 - Metastatic HER2-Positive Breast Cancer 06:46 - Treatment Strategies and Patient Management 11:57 - Maintenance Therapy Options 16:28 - HER2-Positive Breast Cancer Trials 20:13 - Brain Metastases and Systemic Therapy 27:38 - Future Directions in HER2-Positive Breast Cancer --- RESOURCES DESTINY-Breast09 Trial https://www.nejm.org/doi/full/10.1056... PATINA Trial https://www.nejm.org/doi/full/10.1056... HER2CLIMB Trial https://www.nejm.org/doi/full/10.1056... --- BackTable Tumor Board is a multidisciplinary podcast for healthcare professionals that play an active role in cancer care. #ONC48