Managing Brain Metastases in HER2+  Breast Cancer: Second-Line Treatment Decisions

Clinical Brief: Brain Metastases in HER2+ Breast Cancer

Key Themes:

• Brain MRI Practices: Varying approaches to brain MRI timing in HER2+ disease––some clinicians order routinely, others only with symptoms or at progression
• Central Nervous System (CNS) Activity of T-DXd: Growing evidence that T-DXd shows efficacy against brain metastases
• Treatment Decision Influence: Presence of brain metastases may influence treatment selection, especially when choosing between therapies with differential CNS activity

Key Points for Physicians:

• Consider baseline brain MRI for newly diagnosed HER2+ metastatic disease, particularly with widespread disease
• Brain MRI should be considered at treatment change points to inform therapeutic decisions
• T-DXd has shown CNS activity, likely due to the payload crossing the blood-brain barrier after separation from the antibody

Notable Insights:

• Traditional paradigms about large molecules not crossing the blood-brain barrier are being challenged by clinical data
• Clinicians’ practices regarding routine brain MRI in asymptomatic patients vary significantly
• The CNS can remain a sanctuary site even in patients who have achieved a pathologic complete response to primary therapy

Clinical Significance:

The approach to brain metastases in HER2+ breast cancer is evolving with emerging evidence of CNS activity for newer targeted agents, potentially changing the paradigm of when to screen for and how to manage brain metastases in this patient population.