Prognostic impact of extracranial disease control in HER2+ breast cancer-related brain metastases

Background: Brain metastases (BM) are common among HER2+ breast cancer (BC) and prognostic stratification is crucial for optimal management. BC-GPA score and subsequent refinements (modified-GPA, updated-GPA) recapitulate prognostic factors. Since none of these indexes includes extracranial disease control, we evaluated its prognostic value in HER2+ BCBM. Methods: Patients diagnosed with HER2+ BCBM at Istituto Oncologico Veneto-Padova (2002-2021) and Montpellier Cancer Institute (2001-2015) were included as exploratory and validation cohorts, respectively. Extracranial disease control at BM diagnosis (no disease/stable disease/response vs. progressive disease) was evaluated. Results: In the exploratory cohort of 113 patients (median OS 12.2 months), extracranial control (n = 65, 57.5%) was significantly associated with better OS at univariate (median OS 17.7 vs. 8.7 months, p = 0.005) and multivariate analysis after adjustment for BC-GPA (HR 0.61, 95% CI 0.39-0.94), modified-GPA (HR 0.64, 95% CI 0.42-0.98) and updated-GPA (HR 0.63, 95% CI 0.41-0.98). The prognostic impact of extracranial disease control (n = 66, 56.4%) was then confirmed in the validation cohort (n = 117) at univariate (median OS 20.2 vs. 9.1 months, p < 0.001) and multivariate analysis adjusting for BC-GPA (HR 0.41, 95% CI 0.27-0.61), modified-GPA (HR 0.44, 95% CI 0.29-0.67) and updated-GPA (HR 0.42, 95% CI 0.28-0.63). Conclusions: Extracranial disease control provides independent prognostic information in HER2+ BCBM beyond commonly used prognostic scores.