ArticleNPJ precision oncology2025
Epigenetic determinants of an immune-evasive phenotype in HER2-low triple-negative breast cancer.
Article in NPJ precision oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 10 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Influence of HER2-low and HER2-zero status on pathologic complete response and survival in triple-negative breast cancer: a meta-analysis.Frontiers in oncology · 2025Pooled it
- Epigenetic Plasticity in Triple-Negative Breast Cancer: Mechanisms of Therapy Resistance, Biomarkers, and Therapeutic Vulnerabilities.Biomedicines · 2026Review
- Pan-cancer analysis identifies APOC1 as a TAM-derived modulator of adaptive immune resistance and predictor of therapeutic response.Discover oncology · 2026Article
- Distinct immune microenvironment in HER2-low triple-negative breast cancer underlies inferior response to immunotherapy.NPJ precision oncology · 2026Article
- Distinct epigenetic alterations and accelerated mitotic aging define second primary breast cancers.Scientific reports · 2026Article
- Therapy as a State-Generator: Dynamic Phenotypic Landscapes and Adaptive Stress Circuits in Chemotherapy Resistance of Breast Cancer.Antioxidants (Basel, Switzerland) · 2026Review
- Mechanisms of Resistance and Synergy: The Role of Tumor Microenvironment in HER2-Low Breast Cancer Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Neuro-immune interactions in cancer: mechanisms and therapeutic prospects.Frontiers in immunology · 2026Review
- HER2-Low Breast Cancer at the Interface of Pathology and Technology: Toward Precision Management.Biomedicines · 2025Review
- Epigenetic programs shaping lung metastasis in triple-negative breast cancer.Research square · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
14 authors.
Funding
Abstract
Identifying molecular drivers in triple-negative breast cancer (TNBC) is crucial. While HER2-low expression predicts response to novel antibody-drug conjugates, its biological influence on TNBC biology is unknown. We performed a comprehensive multi-omics analysis, integrating genomic, epigenomic, transcriptomic, and proteomic profiling to characterize HER2-low TNBC. We generated genome-wide DNA methylation profiles from a multi-institutional cohort and integrated our data with three independent cohorts (TCGA, SCAN-B, I-SPY2). TNBC cases were categorized as HER2-zero (IHC 0) or HER2-low TNBC (IHC 1+/2+, ISH non-amplified). Among 506 patients (HER2-low, n = 288; HER2-zero, n = 218), HER2-low TNBC exhibited significantly lower tumor mutational burden (P = 0.02). Epigenetic analysis identified 5287 differentially methylated sites, with consistent hypermethylation of HLA genes in HER2-low tumors. Transcriptomic analyses revealed significant downregulation of genes enriched in immune response pathways (e.g., leukocyte activation, T-cell signaling) in HER2-low TNBC (adjusted P < 0.001). Immune cell deconvolution showed reduced immune cell infiltration in the HER2-low tumor microenvironment (P = 0.002). Higher expression of five immune-related genes, downregulated in HER2-low, correlated with improved relapse-free (HR = 0.52; P < 0.001) and overall survival (HR = 0.36; P < 0.001). HER2-low TNBC tumors display distinct molecular features compared to HER2-zero, imparting an immune-evasive phenotype. These findings provide critical insights into the unique biology of HER2-low TNBC, warranting further clinical investigation.
Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.