Brain metastasis as the first and only metastatic relapse site portends worse survival in patients with advanced HER2+ breast cancer

Abstract PurposeCurrent guidelines for patients with HER2+ breast cancer brain metastases (BCBrM) diverge based on the status of extracranial disease (ECD). An in-depth understanding of the impact of ECD on outcomes in HER2+ BCBrM has never been performed. Our study explores the implications of ECD status on intracranial progression-free survival (iPFS) and overall survival (OS) after first incidence of HER2+ BCBrM and radiation.MethodsA retrospective analysis was performed of 153 patients diagnosed with initial HER2+ BCBrM who received radiation therapy to the central nervous system (CNS) at Duke between 2008 and 2020. The primary endpoint was iPFS defined as time from first CNS radiation treatment to intracranial progression or death. OS was defined as time from first CNS radiation or first metastatic disease to death. Systemic staging scans within 30 days of initial BCBrM defined ECD status. ResultsIn this cohort, >70% of patients had controlled ECD with either isolated intracranial relapse (27%) or stable/responding ECD (44%). OS from initial metastatic disease to death was markedly worse for patients with isolated intracranial relapse (median=28.4m) compared to those with progressive or stable/responding ECD (48.8m and 68.1m, respectively, p=0.0035). OS from first CNS radiation to death was significantly worse for patients with progressive ECD (17.8m) versus stable/responding (36.6m) or isolated intracranial relapse (28.4m, p=0.008). iPFS did not differ statistically.ConclusionOS in patients with HER2+ isolated BCBrM was inferior to those with concurrent progressive or stable/responding ECD. Studies investigating initiation of brain penetrable HER2-targeted therapies earlier in the disease course of isolated HER2+ intracranial relapse patients are warranted.