Survival among patients with ERBB2-positive metastatic breast cancer and central nervous system disease Journal Article
| Authors: | Ferraro, E.; Reiner, A. S.; Bou Nassif, R.; Tosi, U.; Brown, S.; Zeller, S.; Dang, C. T.; Seidman, A. D.; Moss, N. S. |
| Article Title: | Survival among patients with ERBB2-positive metastatic breast cancer and central nervous system disease |
| Abstract: | This cohort study explores survival among patients with ERBB2-positive metastatic breast cancer with only central nervous system (CNS) metastasis compared with CNS and extracranial metastases. Key Points: Question: What are the overall and central nervous system (CNS)–related mortality rates among patients with ERBB2-positive metastatic breast cancer with CNS disease only compared with those with both CNS and extracranial metastasis? Findings: In this cohort study of 274 patients with metastatic ERBB2-positive breast cancer and CNS metastasis, those with CNS-only disease had longer overall survival and a lower risk of death from any cause compared with patients with concomitant extracranial metastases. Meaning: The findings suggest that aggressive treatments (both local and systemic) may be warranted to control the intracranial progression of CNS metastases. Importance: Approximately one-third of patients with ERBB2 (formerly HER2 or HER2/neu)–positive (ERBB2<sup>+</sup>) metastatic breast cancer (MBC) develop brain metastasis. It is unclear whether patients with disease limited to the central nervous system (CNS) have different outcomes and causes of death compared with those with concomitant extracranial metastasis. Objective: To assess overall survival (OS) and CNS-related mortality among patients with ERBB2<sup>+</sup> breast cancer and a diagnosis of CNS disease by disease distribution (CNS only vs CNS plus extracranial metastasis). Design, Setting, and Participants: This single-center, retrospective cohort study included patients with ERBB2<sup>+</sup> MBC and CNS disease, including parenchymal brain metastasis, leptomeningeal disease (LMD), or dural metastasis, who were treated between August 2010 and April 2022 at Memorial Sloan Kettering Cancer Center. Data were analyzed between December 2023 and August 2024. Main Outcomes and Measures: Overall survival, estimated with the Kaplan-Meier method, and CNS-related mortality with cumulative incidence. Results: The cohort included 274 patients (272 [99.3%] female). The median age was 53.7 years (range, 28.7-87.4 years); 125 patients (45.6%) presented with de novo MBC. At CNS metastasis diagnosis, 73 (26.6%) presented with CNS-only disease. There was a median follow-up of 3.7 years (range, 0.2-12.0 years) from CNS disease diagnosis among those alive at the end of follow-up. Both OS and CNS-related death were significantly correlated with the pattern of presentation: OS was shortest among patients with LMD (1.24 years; 95% CI, 0.89-2.08 years) followed by those with extracranial metastasis (2.16 years; 95% CI, 1.87-2.58 years) and was longest among patients with parenchymal or dural CNS disease only (3.57 years; 95% CI, 2.10-5.63 years) (P =.001). Of 192 patients (70.1%) who died, 106 (55.2%) died of a CNS-related cause. The group with CNS-only disease remained at high risk of death from CNS causes, with a 3-year CNS-related death rate of 33.98% (95% CI, 22.84%-45.43%) and a 3-year death rate from other causes of 6.07% (95% CI, 1.93%-13.69%). On multivariable modeling for CNS-related death, LMD (hazard ratio, 1.87; 95% CI, 1.19-2.93; P =.007) and treatment with whole-brain radiotherapy (hazard ratio, 1.71; 95% CI, 1.13-2.58; P =.01) were associated with CNS-related death. Conclusions and Relevance: In this cohort study, 55.2% of deaths among patients with ERBB2<sup>+</sup> breast cancer and brain metastasis were due to CNS-related causes, with the greatest risk among patients with LMD. CNS-only presentation was associated with improved survival but a higher rate of CNS-related death, supporting an approach of aggressive local therapy for select patients. |
| Journal Title: | JAMA Network Open |
| Volume: | 8 |
| Issue: | 1 |
| ISSN: | 2574-3805 |
| Publisher: | American Medical Association |
| Date Published: | 2025-01-01 |
| Start Page: | e2457483 |
| DOI: | 10.1001/jamanetworkopen.2024.57483 |
| PROVIDER: | EBSCOhost |
| PROVIDER: | cinahl plus with full text |
| PMCID: | PMC11786230 |
| PUBMED: | 39888615 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Nelson S. Moss -- Source: CINAHL Plus with Full Text |
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