Central nervous system metastases in metastatic breast cancer: Incidence, subtype-specific patterns, and outcomes from the Austrian AGMT_MBC registry.

BACKGROUND: Brain metastases (BM) cause substantial morbidity and reduced survival in metastatic breast cancer (MBC). Therapeutic advances may have altered BM incidence and outcomes across subtypes. Real-world data are crucial to assess these trends and guide BM-specific clinical trials. Here, we report BM data from the Austrian Study Group for Medical Tumor Therapy MBC registry. METHODS: Patients with known hormone receptor (HR) and HER2 status and sufficient outcome data were included. Logistic regression was used to assess the risk of BM. Overall survival (OS) was estimated using Kaplan-Meier methods and compared by log-rank tests. Multivariable Cox models with BM as a time-dependent variable and competing-risk analyses were applied. RESULTS: Among 2775 patients, 477 (17.2%) developed BM during the metastatic course; 56 patients (2.0%) had brain-only disease at first metastatic diagnosis. Compared with luminal MBC, BM risk was higher in HR-/HER2+ (OR 3.57), HR+/HER2+ (OR 4.43), and triple-negative breast cancer (TNBC; OR 2.91). At a median follow-up of 77 months, BM were associated with significantly shorter OS (HR 4.23; p < 0.001). TNBC showed the shortest BM-free survival (7.1 months) and poorest OS after BM diagnosis (4.7 months). Brain-only disease was associated with improved OS compared to concurrent extracranial disease (HR 0.58; p = 0.001). Use of whole brain radiotherapy declined over time, while neurosurgery or focal radiotherapy were associated with longer OS. Receptor discordance included HR loss (14.5%) and HER2 gain (9.8%). CONCLUSION: BM remain frequent and prognostically relevant in MBC, underscoring the need for improved risk stratification and subtype-specific therapies.