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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
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...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10382984/ https://www.ncbi.nlm.nih.gov/pubmed/37419078 http://dx.doi.org/10.1016/j.breast.2023.06.005 |
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author | Zaakouk, Mohamed Quinn, Cecily Provenzano, Elena Boyd, Clinton Callagy, Grace Elsheikh, Soha Flint, Joe Millican-Slater, Rebecca Gunavardhan, Anu Mir, Yasmeen Makhija, Purnima Di Palma, Silvana Pritchard, Susan Tanchel, Bruce Rakha, Emad Atallah, Nehal M. Lee, Andrew H.S. Pinder, Sarah Shaaban, Abeer M. |
author_facet | Zaakouk, Mohamed Quinn, Cecily Provenzano, Elena Boyd, Clinton Callagy, Grace Elsheikh, Soha Flint, Joe Millican-Slater, Rebecca Gunavardhan, Anu Mir, Yasmeen Makhija, Purnima Di Palma, Silvana Pritchard, Susan Tanchel, Bruce Rakha, Emad Atallah, Nehal M. Lee, Andrew H.S. Pinder, Sarah Shaaban, Abeer M. |
author_sort | Zaakouk, Mohamed |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10382984 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-103829842023-07-30 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 Makhija, Purnima Di Palma, Silvana Pritchard, Susan Tanchel, Bruce Rakha, Emad Atallah, Nehal M. Lee, Andrew H.S. Pinder, Sarah Shaaban, Abeer M. Breast Original Article 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. Elsevier 2023-06-27 /pmc/articles/PMC10382984/ /pubmed/37419078 http://dx.doi.org/10.1016/j.breast.2023.06.005 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Original Article Zaakouk, Mohamed Quinn, Cecily Provenzano, Elena Boyd, Clinton Callagy, Grace Elsheikh, Soha Flint, Joe Millican-Slater, Rebecca Gunavardhan, Anu Mir, Yasmeen Makhija, Purnima Di Palma, Silvana Pritchard, Susan Tanchel, Bruce Rakha, Emad Atallah, Nehal M. Lee, Andrew H.S. Pinder, Sarah Shaaban, Abeer M. 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10382984/ https://www.ncbi.nlm.nih.gov/pubmed/37419078 http://dx.doi.org/10.1016/j.breast.2023.06.005 |
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