ArticleESMO open2025
Interobserver consistency and diagnostic challenges in HER2-ultralow breast cancer: a multicenter study.
Article in ESMO open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Revisiting HER2-negative breast cancer in the era of HER2-low and HER2-ultralow expression: Assessment of interobserver variability.Breast (Edinburgh, Scotland) · 2026Article
- 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
- Article
- Deep learning-based assessment of HER2-ultralow expression in breast cancer: a multi-center validation study across primary and metastatic lesions.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
- Repurposing HER2 IHC: Pan-HER2 and Low-HER2.Applied immunohistochemistry & molecular morphology : AIMM · 2026Review
- Digital image analysis improves diagnostic accuracy of HER2-low and HER2-ultralow breast cancer: a step towards personalised medicine.Virchows Archiv : an international journal of pathology · 2026Article
- Quantitative immunohistochemistry and the use of cellular calibrators for HER2 receptor number determination.Scientific reports · 2026Article
- Prevalence of HER2-ultralow breast cancer in South Korea: a multicenter study by reassessment of HER2-zero cases.Journal of pathology and translational medicine · 2026Article
- Predictive Biomarkers of Antibody-Drug Conjugate Efficacy for Solid Tumors: Current Challenges and the Potential Role of Quantitative Proteomics.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Review
- Artificial Intelligence-Driven Quantitative HER2 Scoring and Spatial Bystander Effect Modeling for ADC Response Stratification in HER2-Low Breast Cancer.Breast cancer (Dove Medical Press) · 2026Review
- Redefining HER2 in Breast Cancer: From Conventional Positivity to Low and Ultralow in the New Era of Antibody-Drug Conjugates.Cancer research and treatment · 2026Review
- HER2 Heterogeneity in Breast Cancer: Biological Basis, Clinical Implications, and Therapeutic Strategies.Breast cancer (Dove Medical Press) · 2026Review
- HER2-Low Breast Cancer at the Interface of Pathology and Technology: Toward Precision Management.Biomedicines · 2025Review
- Liquid Biopsy and Multi-Omic Biomarkers in Breast Cancer: Innovations in Early Detection, Therapy Guidance, and Disease Monitoring.Biomedicines · 2025Review
- New standards in HER2-low testing: the CASI-01 comparative methods study.EBioMedicine · 2025Article
- AI-driven MRI biomarker for triple-class HER2 expression classification in breast cancer: a large-scale multicenter study.Breast cancer research : BCR · 2025Article
- Transformer-BasedDiagnostics (Basel, Switzerland) · 2025Article
- HER2-Low Breast Cancer-Current Knowledge and Future Directions.Medicina (Kaunas, Lithuania) · 2025Review
- Prevalence and concordance of HER2-low and HER2-ultralow status between historical and rescored results in a multicentre study of breast cancer patients in China.Breast cancer research : BCR · 2025Article
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Authors and funding
23 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRecent advancements in novel antibody-drug conjugates (ADCs) have demonstrated efficacy in patients with human epidermal growth factor receptor 2 (HER2)-ultralow breast cancer (BC), expanding the eligibility for anti-HER2 targeted therapy to include some patients previously categorized as HER2 immunohistochemistry (IHC) 0. This expansion underscores the need for pathologists to accurately differentiate HER2-null and HER2-ultralow. MATERIALS AND
methodsThirty-six pathologists from four centers nationwide conducted microscopic visual assessments on HER2 IHC slides from 50 consecutive BC surgical specimens, all previously diagnosed as HER2 IHC 0.
resultsThe interobserver consistency in differentiating HER2-null from HER2-ultralow, measured by Fleiss κ, was only 0.230-lower than the consistency for combined HER2 IHC 0 cases (Fleiss κ = 0.344) and binary classification (HER2-null versus HER2-non-null; Fleiss κ = 0.292). High agreement for HER2-null versus HER2-ultralow differentiation was achieved in only 4% of cases, while combining them into HER2 IHC 0 raised high agreement cases to 32%, higher than the 18% seen in the binary classification. Consensus among the 36 pathologists aligned with historical scores in 72% of cases; however, when subdividing HER2 IHC 0 into HER2-null and HER2-ultralow, the consistency dropped to 54%.
conclusionsThe low consistency among pathologists in distinguishing HER2-null, -ultralow, and 1+ cases may impact patient eligibility for new ADC therapies. To address this challenge, there is a need for improved detection methods, artificial intelligence-assisted quantitative assessments, and larger clinical datasets to refine the definition of HER2-ultralow.
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