Concordance of HER2-low scoring in breast carcinoma among expert pathologists in the United Kingdom and the republic of Ireland -on behalf of the UK national coordinating committee for breast pathology
Zaakouk, Mohamed Quinn, Cecily Provenzano, Elena Boyd, Clinton Callagy, Grace Elsheikh, Soha Flint, Joe Millican-Slater, Rebecca Gunavardhan, Anu Mir, Yasmeen
Zaakouk, Mohamed
Quinn, Cecily
Provenzano, Elena
Boyd, Clinton
Callagy, Grace
Elsheikh, Soha
Flint, Joe
Millican-Slater, Rebecca
Gunavardhan, Anu
Mir, Yasmeen
Abstract
Background: Recent clinical evidence showed that breast cancer with low HER2 expression levels responded to trastuzumab deruxtecan therapy. The HER2-low cancers comprise immunohistochemistry (IHC) score 1+ and 2+ ISH non-amplified tumours, currently classified as HER2 negative. Little data exists on the reproducibility of pathologists reporting of HER2-low cancer.
Patient and methods: Sixteen expert pathologists of the UK National Coordinating Committee for Breast Pathology scored 50 digitally scanned HER2 IHC slides. The overall level of agreement, Fleiss multiple-rater kappa statistics and Cohen's Kappa were calculated. Cases with low concordance were re-scored by the same pathologists after a washout period.
Results: Absolute agreement was achieved in 6% of cases, all of which scored 3+. Poor agreement was found in 5/50 (10%) of cases. This was due to heterogeneous HER2 expression, cytoplasmic staining and low expression spanning the 10% cut-off value. Highest concordance (86%) was achieved when scores were clustered as 0 versus others. Improvement in kappa of overall agreement was achieved when scores 1+ and 2+ were combined. Inter-observer agreement was moderate to substantial in the whole cohort but fair to moderate in the HER2-low group. Similarly, consensus-observer agreement was substantial to almost perfect in the whole cohort and moderate to substantial in the HER2-low group.
Conclusion: HER2-low breast cancer suffers from lower concordance among expert pathologists. While most cases can reproducibly be classified, a small proportion (10%) remained challenging. Refining the criteria for reporting and consensus scoring will help select appropriate patients for targeted therapy.
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Date
2023-06-27
Type
Article
Subject
Oncology. Pathology.
Collections
Citation
Zaakouk M, Quinn C, Provenzano E, Boyd C, Callagy G, Elsheikh S, Flint J, Millican-Slater R, Gunavardhan A, Mir Y, Makhija P, Di Palma S, Pritchard S, Tanchel B, Rakha E, Atallah NM, Lee AHS, Pinder S, Shaaban AM. Concordance of HER2-low scoring in breast carcinoma among expert pathologists in the United Kingdom and the republic of Ireland -on behalf of the UK national coordinating committee for breast pathology. Breast. 2023 Aug;70:82-91. doi: 10.1016/j.breast.2023.06.005. Epub 2023 Jun 27. PMID: 37419078; PMCID: PMC10382984.
Journal / Source Title
Breast
DOI
10.1016/j.breast.2023.06.005
PMID
37419078
Publisher
Elsevier
Publisher’s URL
https://www.sciencedirect.com/journal/the-breast