{"title":"乳腺癌病理学家对人表皮生长因子受体2 （HER2）免疫组化评分的准确性，包括HER2低截止点：乳腺癌中HER2免疫组化评分一致性","authors":"Agata Wróbel, Michel Vandenberghe, Marietta Scott, Frances Jones, Tsuyoshi Matsuo, Anne-Marie Boothman, Jessica Whiteley, Craig Barker","doi":"10.1186/s13000-025-01624-3","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Breast 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.</p><p><strong>Objective: </strong>To assess HER2-low and HER2-ultralow scoring performance by pathologists, and compare real-world HER2-low scoring with centralized scoring by trained pathologists.</p><p><strong>Methods: </strong>Formalin-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+).</p><p><strong>Results: </strong>Substantial 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).</p><p><strong>Conclusions: </strong>Pathologists 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.</p>","PeriodicalId":11237,"journal":{"name":"Diagnostic Pathology","volume":"20 1","pages":"35"},"PeriodicalIF":2.4000,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969812/pdf/","citationCount":"0","resultStr":"{\"title\":\"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.\",\"authors\":\"Agata Wróbel, Michel Vandenberghe, Marietta Scott, Frances Jones, Tsuyoshi Matsuo, Anne-Marie Boothman, Jessica Whiteley, Craig Barker\",\"doi\":\"10.1186/s13000-025-01624-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Breast 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.</p><p><strong>Objective: </strong>To assess HER2-low and HER2-ultralow scoring performance by pathologists, and compare real-world HER2-low scoring with centralized scoring by trained pathologists.</p><p><strong>Methods: </strong>Formalin-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+).</p><p><strong>Results: </strong>Substantial 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).</p><p><strong>Conclusions: </strong>Pathologists 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.</p>\",\"PeriodicalId\":11237,\"journal\":{\"name\":\"Diagnostic Pathology\",\"volume\":\"20 1\",\"pages\":\"35\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2025-04-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969812/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diagnostic Pathology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13000-025-01624-3\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PATHOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diagnostic Pathology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13000-025-01624-3","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PATHOLOGY","Score":null,"Total":0}
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.
Background: Breast 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.
Objective: To assess HER2-low and HER2-ultralow scoring performance by pathologists, and compare real-world HER2-low scoring with centralized scoring by trained pathologists.
Methods: Formalin-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+).
Results: Substantial 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).
Conclusions: Pathologists 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.
期刊介绍：
Diagnostic Pathology is an open access, peer-reviewed, online journal that considers research in surgical and clinical pathology, immunology, and biology, with a special focus on cutting-edge approaches in diagnostic pathology and tissue-based therapy. The journal covers all aspects of surgical pathology, including classic diagnostic pathology, prognosis-related diagnosis (tumor stages, prognosis markers, such as MIB-percentage, hormone receptors, etc.), and therapy-related findings. The journal also focuses on the technological aspects of pathology, including molecular biology techniques, morphometry aspects (stereology, DNA analysis, syntactic structure analysis), communication aspects (telecommunication, virtual microscopy, virtual pathology institutions, etc.), and electronic education and quality assurance (for example interactive publication, on-line references with automated updating, etc.).
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