Clinical Insights on the Next Treatment Approach for Metastatic HER2+  Breast Cancer with Brain Metastasis

Clinical Brief: Case Presentation – HER2-Positive Disease with Brain Metastases

Key Themes:

• Case Presentation: 47-year-old with initially early-stage HER2-positive/hormone receptor–negative (HER2+/HR–) breast cancer who developed brain metastases along with systemic disease 12 months after completing adjuvant therapy
• Treatment Approach: Patient received stereotactic radiosurgery for brain metastases followed by paclitaxel, trastuzumab, and pertuzumab, then trastuzumab deruxtecan (T-DXd) upon progression
• Management of Treatment Complications: Patient developed grade 1 interstitial lung disease with T-DXd; treatment was interrupted until resolution, then resumed

Key Points for Physicians:

• HER2+/HR– disease may have a higher risk of central nervous system (CNS) recurrence than HR+ disease
• Treatment sequencing typically includes local therapy for symptomatic brain metastases followed by systemic therapy
• The HER2CLIMB regimen (tucatinib, capecitabine, trastuzumab) is appropriate after progression on T-DXd, especially with brain metastases

Notable Insights:

• Despite being low risk (stage I, node negative), the patient relapsed quickly with extensive metastatic disease including brain involvement
• The case highlights the value of multidisciplinary discussion for patients with brain metastases
• Different radiation oncologists may have varying approaches to brain metastases––some prefer up front SRS while others favor systemic therapy with CNS activity

Clinical Significance:

Management of HER2+ breast cancer with brain metastases requires a multidisciplinary approach. Increasing evidence supports systemic therapies with CNS activity as important components of treatment, potentially changing the traditional paradigm of local therapy followed by systemic treatment.