1. 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
- Author
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Mohamed Zaakouk, Cecily Quinn, Elena Provenzano, Clinton Boyd, Grace Callagy, Soha Elsheikh, Joe Flint, Rebecca Millican-Slater, Anu Gunavardhan, Yasmeen Mir, Purnima Makhija, Silvana Di Palma, Susan Pritchard, Bruce Tanchel, Emad Rakha, Nehal M. Atallah, Andrew H.S. Lee, Sarah Pinder, and Abeer M. Shaaban
- Subjects
Breast cancer ,HER2-Low ,HER2-Ultralow ,Consistency ,Concordance ,Immunohistochemistry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - 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.
- Published
- 2023
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