Prediction of Outcomes of Brain Irradiation in Correlation with Molecular Subtypes in Patients with Metastatic Breast Cancer

BACKGROUND: Brain metastases (BM) are a major complication in metastatic breast cancer, especially in HER2-positive and triple-negative subtypes. Despite advances in systemic therapy, BM remains associated with a poor prognosis and often requires radiotherapy. This study evaluates the outcomes of brain irradiation across subtypes and proposes a prognostic scoring system to guide treatment. METHODS: This retrospective study analyzed data from 348 breast cancer patients with BM to develop a prognostic scoring system for radiotherapy decisions. The data included molecular subtypes, number of brain lesions, and survival outcomes. Kaplan-Meier and Cox proportional hazards models were used to identify prognostic factors. The scoring system, based on the significance of predictors, was compared with physician-selected radiotherapy techniques to assess its potential for optimizing care. RESULTS: Luminal breast cancer was most prevalent (42.6%), followed by HER2-positive and triple-negative (19% each). Median BM onset was 23 months; headache was the most common symptom (48%). HER2-positive and triple-negative patients developed metastases earlier than luminal and triple-positive (P=0.001). Survival was better for luminal and triple-positive, poorer for HER2-positive and triple-negative. Patients with fewer than five brain lesions had higher survival rates (P=0.001). The scoring system incorporated molecular subtype, lesion burden, and patient characteristics. Scores above 3.5 predicted worse survival, with higher scores strongly linked to poorer outcomes (P=0.001). CONCLUSION: This study identifies key prognostic factors influencing survival in breast cancer patients with BM and proposes a scoring system to guide radiotherapy decisions. Molecular subtypes, metastatic burden, and clinical characteristics significantly affect outcomes, with HER2-positive and triple-negative subtypes showing the poorest survival. The system provides a structured approach for treatment selection, though further validation is needed to ensure its accuracy and clinical utility in personalized radiotherapy planning.