Brain-only metastatic breast cancer as a distinct clinical entity: evidence from national and institutional cohorts with implications for radiation therapy.

Authors

Marshall Harrell, Tugce Kutuk, Yevgeniya Gokun, Rituraj Upadhyay, Sachin R Jhawar, Daniel Stover, Nicole Williams, Margaret E Gatti-Mayes, Gina Sizemore, Heather LeFebvre, John C Grecula, Raju R Raval, Raj Singh, Simeng Zhu, Dukagjin M Blakaj, Arnab Chakravarti, Joshua D Palmer, Sasha J Beyer

Published in

Breast cancer research and treatment. Volume 219. Issue 3. Oct 07, 2026. Epub Oct 07, 2026.

Abstract

Brain-only metastatic breast cancer (BO-MBC), defined as breast cancer with brain metastases (BrM) in the absence of extracranial metastatic disease (ECM), may represent a distinct metastatic phenotype. We characterized clinicopathologic features, treatment patterns, and outcomes of BO-MBC and evaluated associations between metastatic pattern, treatment, and survival.
Patients with isolated BrM at our institution were evaluated for intracranial progression-free survival (iPFS), extracranial progression-free survival (ePFS), leptomeningeal disease-free survival (LMD-PFS), and overall survival (OS). Patients with MBC diagnosed between 2010 and 2020 were identified from the NCDB and classified as BO-MBC or BrM with concurrent ECM (BrM + ECM). Overlap propensity score-weighted Cox models evaluated associations between metastatic pattern, treatment, and OS.
In the institutional cohort (n = 30), intracranial progression was the predominant pattern of failure, with median iPFS of 14.6 months versus ePFS of 30.4 months. In the NCDB cohort (n = 8,909), 1,540 patients (17.3%) had BO-MBC. Compared with BrM + ECM, BO-MBC was associated with node-negative, triple-negative, and fewer HR+/HER2- disease (p < 0.001). BO-MBC patients were more likely to receive brain radiotherapy (54.8% vs. 41.0%, p < 0.001) but less likely to receive systemic therapy (67.2% vs. 74.5%, p < 0.001). In unadjusted Kaplan-Meier analyses, BO-MBC was associated with longer median OS than BrM + ECM (12.5 months [95% CI, 3.6-43.6] vs. 10.6 months [95% CI, 2.6-33.8]). Systemic therapy was associated with improved OS, with the greatest benefit in BO-MBC (adjusted HR 0.22, 95%CI 0.18-0.27). Brain radiotherapy was associated with improved OS in BO-MBC but not BrM + ECM.
BO-MBC may represent a distinct clinical subgroup with unique clinicopathologic characteristics, treatment patterns, and improved survival. Intracranial progression predominated despite durable extracranial control, supporting optimized brain-directed management and prospective investigation of BO-MBC as a unique metastatic phenotype.
Not applicable.

PMID:
42842025
Bibliographic data and abstract were imported from PubMed on 08 Oct 2026.

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