The treatment landscape for HER2-positive metastatic breast cancer (MBC) has expanded dramatically, with numerous targeted therapies across multiple drug classes significantly improving survival outcomes. However, optimizing treatment selection and sequencing remains challenging, particularly as patients progress through multiple lines of therapy where consensus on preferred regimens becomes less defined. Recent advances have further complicated treatment decisions while providing new opportunities for tailored approaches. In this activity, leading experts provide a comprehensive overview of treatment selection and sequencing for HER2-positive MBC, with specific focus on second-line and beyond therapies. Topics include mechanisms of action across different drug classes, key features of newer treatments including CNS penetrance and tolerability profiles, interpretation of current evidence-based clinical guidelines, and practical strategies for matching regimens to diverse patient populations..

Course Director: Barbara O’Brien, MD
Course Faculty: Alexandra S. Zimmer, MD, MSc 

Brain metastases (BMs) remain a significant source of mortality in HER2-positive metastatic breast cancer, with up to 50% of patients developing BMs often during first-line treatment, yet until recently most clinical trials excluded these patients from study. Recent pivotal trials have begun to reshape this landscape, offering new evidence-based approaches for this challenging clinical scenario. In this activity, leading experts discuss complex patient cases highlighting diverse brain metastasis presentations in HER2-positive MBC, exploring increasing BM incidence, treatment challenges, and breakthrough systemic therapies with promising intracranial efficacy. Topics include identification protocols, evolving perspectives on systemic versus localized approaches, clinical advances with novel regimens, monitoring strategies, and future considerations for brain metastasis prevention.

Course Director: Barbara O’Brien, MD
Course Faculty: Rashmi K. Murthy, MD, MBE and Alexandra S. Zimmer, MD, MSc

Individualizing treatment for patients with HER2-positive metastatic breast cancer (MBC) requires careful consideration of multiple factors, particularly as they progress through successive lines of therapy and develop challenging complications such as brain metastases. While guidelines provide direction for early treatment lines, optimal sequencing beyond second-line therapy becomes increasingly complex as clinicians must consider patient heterogeneity, treatment history, metastatic disease location, and potential adverse events. In this activity, leading experts will examine diverse patient vignettes that reflect real-world clinical challenges in HER2-positive MBC management, including cases featuring brain metastases. Topics include key factors influencing treatment selection across therapy lines, approaches to defining disease progression in both systemic and brain metastases, strategies for anticipating and managing treatment-related adverse events, and practical considerations for later-line therapy where optimal sequencing remains undefined. Through these case discussions, participants will gain valuable insights into creating personalized treatment plans that address the unique needs of each patient.

Course Director: Barbara O’Brien, MD
Course Faculty: Alexandra S. Zimmer, MD, MSc