Brain Metastasis Patterns Affect Breast Cancer Survival

TOPLINE:

In patients with ERBB2-positive metastatic breast cancer (ERBB2+ MBC) and brain metastasis, more than half of deaths were due to central nervous system (CNS)–related causes; however, patients with CNS-only metastasis have significantly longer overall survival than those with both CNS and extracranial metastasis.

METHODOLOGY:

• About one third of patients with ERBB2+ MBC develop brain metastasis, but it is unclear whether survival outcomes differ among patients who have CNS-only metastasis and those with both CNS and extracranial metastasis.
• Researchers analyzed 274 patients with ERBB2+ MBC and brain metastasis (median age, 53.7 years at CNS metastasis diagnosis) who received treatment between August 2010 and April 2022.
• Of all patients, 26.6% (n = 73) had CNS-only metastasis, whereas 72.6% (n = 199) had concomitant extracranial metastasis; two patients had unknown status of extracranial disease. About 94.5% of patients had parenchymal brain metastasis; 15.8% had concomitant leptomeningeal disease.
• The primary outcomes were CNS-related mortality and overall survival, which were calculated from the date of CNS disease diagnosis until death or last follow-up. The median follow-up was 3.7 years.
• About 92.7% of patients received CNS-directed radiotherapy: 40.1% received stereotactic radiosurgery only, 37.2% received whole-brain radiotherapy only, and 15.3% received both.

TAKEAWAY:

• Patients with CNS-only disease had significantly longer overall survival compared with those with concomitant extracranial metastasis (3.48 years vs 1.96 years; P = .02). At 5 years, 38.43% of patients in the CNS-only group and 23.70% in the concomitant group were alive.
• Among the 192 patients who died, 55.2% deaths were CNS-related. Patients had a high 3-year rate of CNS-related death overall (32.52%), and this rate did not differ significantly between patients who had CNS-only disease (33.98%) vs those with both CNS and extracranial metastasis (31.76%). However, those with CNS-only disease had a much lower 3-year rate of death from other causes compared with those with both CNS and extracranial metastasis (6.07% for CNS-only vs 32.55% for both).
• Leptomeningeal disease (hazard ratio [HR], 1.87) and whole-brain radiotherapy (HR, 1.71) were significantly associated with increased risk for CNS-related death.
• Patients with parenchymal or dural metastasis only had longer overall survival (3.57 years) than those with concomitant extracranial metastases (2.16 years) or leptomeningeal disease (1.24 years).

IN PRACTICE:

“In this cohort study of 274 patients with ERBB2+ MBC and brain metastasis, CNS progression was the most common cause of death,” the authors wrote, adding that “patients with CNS-only disease experienced longer survival than those with concomitant extracranial metastasis but still had significant CNS-related mortality.”

SOURCE:

This study, led by Emanuela Ferraro, MD, Memorial Sloan Kettering Cancer Center in New York City, was published online in JAMA Network Open, alongside an accompanying editorial.

LIMITATIONS:

The retrospective, single-center design may limit generalizability. Additionally, the definition of CNS-related death relied on clinical records, which could have introduced misclassification bias. Neurologic outcomes and quality of life were not evaluated.

DISCLOSURES:

This study was funded by a Cancer Center Support grant from the National Cancer Institute, National Institutes of Health. Ferraro disclosed receiving salary support from the 2022-2024 Terri Brodeur Breast Cancer Foundation award. Some other authors reported having various affiliations with multiple sources. Additional disclosures are available in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.