ArticleDiagnostic pathology2025
Accuracy of human epidermal growth factor receptor 2 (HER2) immunohistochemistry scoring by pathologists in breast cancer, including the HER2-low cutoff : HER2 IHC scoring concordance in breast cancer.
Article in Diagnostic pathology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
9 citing papers in PubMed.
- Diagnostic reproducibility, spatial heterogeneity, and survival outcomes of HER2-Null, HER2-Ultralow, and HER2-Low categories in invasive breast carcinoma.Virchows Archiv : an international journal of pathology · 2026Article
- Trastuzumab Deruxtecan for HER2-Low Metastatic Breast Cancer: Practical Considerations for Medical Oncologists and Pathologists in Australia.Asia-Pacific journal of clinical oncology · 2026Review
- The critical role of accurate neoplastic cell percentage (NCP) assessment: investigating targeted training strategies for pulmonary biopsy and cytology specimens.Virchows Archiv : an international journal of pathology · 2026Article
- HER2-low and ultralow breast cancer: interobserver challenges and lessons from a consensus study.Journal of pathology and translational medicine · 2026Article
- Mechanisms of Resistance and Synergy: The Role of Tumor Microenvironment in HER2-Low Breast Cancer Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- "HER2-Low" and the Challenge of Repurposing Legacy HER2 IHC Biomarker Assays.Current oncology (Toronto, Ont.) · 2026Article
- Transformer-BasedDiagnostics (Basel, Switzerland) · 2025Article
- Human Epidermal Growth Factor Receptor 2-Low Breast Cancer: Prevalence Rate and Scoring Concordance Among Pathologists.Breast cancer : basic and clinical research · 2025Article
- Fully Automated Stain Quantification Framework for IHC Whole Slide Images in Breast Cancer.Technology in cancer research & treatmentArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBreast cancer was previously categorized as human epidermal growth factor receptor 2 (HER2)-positive (immunohistochemistry [IHC] 3+, IHC 2+ / in situ hybridization [ISH]-positive) or HER2-negative (IHC 0, IHC 1+, IHC 2+/ISH-). Recent studies of trastuzumab deruxtecan, a HER2-directed antibody-drug conjugate, have explored the spectrum of HER2 expression in tumors categorized as HER2-negative, including HER2-low (IHC 1+, IHC 2+/ISH-) and HER2-ultralow (IHC 0 with membrane staining). Clinical relevance of HER2-low and HER2-ultralow is reinforced by encouraging efficacy findings in these populations.
objectiveTo assess HER2-low and HER2-ultralow scoring performance by pathologists, and compare real-world HER2-low scoring with centralized scoring by trained pathologists.
methodsFormalin-fixed, paraffin-embedded breast cancer samples stained by the VENTANA anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody (Roche) assay were selected to ensure adequate representation across all HER2 IHC scores (N = 500). Samples were rescored in a central laboratory by three pathologists trained in HER2-low scoring, and a majority consensus generated. Agreement between consensus and historical real-world HER2 scores was assessed by Fleiss' kappa across HER2 scores (IHC 0, 1+, 2+, 3+).
resultsSubstantial agreement was observed among central pathologists across HER2 scores (κ = 0.69), for the HER2-low cutoff (IHC 0 vs. IHC 1+, 2+, 3+; κ = 0.79), and the HER2-ultralow cutoff (IHC 0 absent membrane staining vs. IHC 0 with membrane staining, 1+, 2+, 3+; κ = 0.68). Substantial agreement was observed between real-world pathologists and central consensus for the HER2-low cutoff (κ = 0.72).
conclusionsPathologists can reproducibly score HER2-low and HER2-ultralow when supported by training. Findings may aid decision-making for patients with breast cancer who are potentially eligible for HER2-directed therapy.
Indexed as
Identifiers
What OpenQuestion holds
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.