Subtype-Specific Risk and Temporal Dynamics of Brain Metastases in Metastatic Breast Cancer

Abstract

Background: Despite advancements in breast cancer treatments, brain metastases (BM) remain a major clinical challenge in metastatic breast cancer (MBC), adversely affecting survival and quality of life. This study investigates the lifetime incidence, temporal trends, and survival outcomes of BM across different breast cancer subtypes in patients with MBC. Patients and Methods: We retrospectively analyzed a database of 2311 MBC patients treated between 2005 and 2024 at Yonsei Cancer Center and Gangnam Severance Hospital in Korea. Clinical, radiologic, and molecular data were extracted from the institutional database. BM incidence rates were compared across subtypes. Survival outcomes were analyzed based on BM burden and local treatment strategies. Results: BM developed in 22.7% (525/2311) of MBC patients throughout the disease course. The incidence was highest in HER2-positive(+) (34.2%) and triple-negative breast cancer (TNBC) (33.0%) subtypes, while significantly lower in HR +/HER2- breast cancer (14.4%). The annual incidence of BM showed an early peak pattern, with 94.7% of TNBC cases and 82.2% of HER2 + cases occurring within the first 3 years of metastatic disease. In contrast, HR+/HER2- cases showed no distinct peak pattern over time. Survival outcomes were closely linked to tumor burden, including the number of BM lesions (P < .0001) and the presence of symptoms (P = .021). Conclusion: This study highlights the high risk of early BM in HER2 + and TNBC subtypes, with most cases occurring within the first 3 years of metastatic disease. These findings support the need for early surveillance strategies in these high-risk groups to enable timely detection and intervention. (c) 2026 Published by Elsevier Inc.