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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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, and Shaaban, Abeer M.
- Subjects
COHEN'S kappa coefficient (Statistics) ,PATHOLOGISTS - Abstract
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. 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. 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. 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. • Concordance of HER2 low scoring using digital whole slide images was assessed among 16 expert pathologists. • 10% of cases were challenging to classify; all were of the HER2 low and ultralow. • Heterogeneity, cytoplasmic expression and percentage expression around 10% were reasons for discordance. • Clustering of categories (0 versus others) resulted in the highest concordance levels. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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