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This slideset with an accompanying video module examines the rapidly evolving treatment landscape for HER2-positive metastatic breast cancer, focusing on evidence from key clinical trials that are reshaping first-line therapy, maintenance strategies, and treatment sequencing. Explore how emerging data on HER2-directed therapies inform individualized treatment decisions, including when to incorporate T-DXd, tucatinib, and other targeted approaches, how to navigate limited evidence following T-DXd progression, and how to integrate systemic and local therapies for patients with CNS metastases.