ArticleNeuro-oncology2025
Analysis of HER2 expression changes from breast primary to brain metastases and the impact of HER2-low expression on overall survival.
Article in Neuro-oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Soluble HER2 promotes chronic antigen-mediated CD8⁺ T-cell dysfunction and limits immunotherapy response in HER2-low triple-negative breast cancer.Cell death & disease · 2026Article
- The Current Landscape of Metastatic Breast Cancer: A Pathology Guide on Emerging Biomarkers.Cancers · 2026Review
- Trastuzumab deruxtecan efficacy, FcRn-facilitated penetration of the blood-tumor barrier, and distribution to tumor cells in HER2+ brain metastasis model systems.Neuro-oncology · 2026Article
- Characterization of HER2-Positive Murine Breast Cancer Models for Investigating HER2-Targeted Therapy and Immunotherapy.Cancers · 2026Article
- Antibody-drug conjugates in cancer therapy: current landscape, challenges, and future directions.Molecular cancer · 2025Review
- Antibody drug conjugates in metastatic brain tumors: current landscape, therapeutic potential and challenges.Journal of neuro-oncology · 2025Review
- Case Report: Unlocking opportunities in HER2-targeted antibody-drug conjugates for bulky leptomeningeal metastatic breast cancer.Frontiers in oncology · 2025Article
- Review
- A potential central nervous system niche for trastuzumab deruxtecan in patients with HER2-expressing non-small cell lung cancer.Translational lung cancer research · 2024Article
- Role of antibody drug conjugates in the treatment of patients with breast cancer brain metastases.Therapeutic advances in medical oncology · 2024Review
- HR+/HER2- breast cancer brain metastases treated with definitive local therapy: a focus on endocrine sensitivity and incidence of leptomeningeal disease.Neuro-oncology advancesArticle
- Excellent Response to Trastuzumab Deruxtecan of a Large Medullary Metastasis from Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: A Case Report.Case reports in oncologyArticle
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Authors and funding
14 authors.
Funding
Abstract
backgroundThere are limited data regarding HER2-low expression dynamics between matched primary tumors and brain metastases (BrMs) in breast cancer. HER2-low expression has emerged as a new therapeutic biomarker for highly active antibody-drug conjugates with emerging intracranial activity.
methodsPatients with metastatic breast cancer and BrMs seen at an NCI-designated center between 2003 and 2023 were identified. HER2 expression was defined as HER2-positive (3+, 2+/ISH amplified), HER2-low (1+, 2+/ISH negative), or HER2-0 by ASCO-CAP guidelines. Estrogen receptor (ER) status was defined as ER ≥1%. Multivariate survival analyses by Cox proportional hazard models were determined from the time of BrM resection to death or last follow-up between the 3 subtypes, controlling for ER and age.
resultsAmong 197 matched primary and resected BrMs, 81% exhibited HER2 expression in the brain: 61% HER2-positive, 20% HER2-low, and 19% HER2-0. Concordance was high in HER2-positive primary tumors with 100% retaining HER2 expression (97% retained HER2-positive expression and 2.7% switched to HER2-low). HER2-0 primaries frequently showed HER2 gain in BrMs to HER2-low (35%) or HER2-positive (5.4%) status. Among 48 HER2-low primary tumors, 52% were discordant for HER2 status in the brain with 21% testing HER2-positive and 31% testing HER2-0. In adjusted analyses, patients with HER2-positive BrMs had significantly lower death risk than patients with HER2-low BrMs (HR = 0.41, P = .0006); no difference was observed between HER2-0 and HER2-low.
conclusionsIn this retrospective analysis, HER2 expression is common in breast cancer BrMs, emphasizing the need for improved, noninvasive diagnostics. Patients with HER2-low and HER2-0 BrMs face inferior survival, presenting an unmet clinical need.
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