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

• DOI: 10.1016/j.breast.2023.06.005
• Publication Date: 2023-06-27T06:47:39Z
• Authors: Mohamed Zaakouk; Cecily Quinn; Elena Provenzano; Clinton Boyd; Grace Callagy; Soha Elsheikh; Joe Flint; Rebecca Millican-...; Anu Gunavardhan; Yasmeen Mir; Purnima Makhija; Silvana Di Palma; Susan Pritchard; Bruce Tanchel; Emad Rakha; Nehal M. Atallah; Andrew H.S. Lee; Sarah Pinder; Abeer M. Shaaban
• Keywords: Concordance; Kappa

BackgroundRecent 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 negative. Little data exists on the reproducibility of pathologists reporting cancer.Patient methodsSixteen expert UK National Coordinating Committee for Breast Pathology scored 50 digitally scanned IHC slides. overall level agreement, Fleiss multiple-rater kappa statistics Cohen's Kappa were calculated. Cases concordance re-scored by same after a washout period.ResultsAbsolute agreement was achieved in 6% cases, all which 3+. Poor found 5/50 (10%) cases. This due heterogeneous expression, cytoplasmic staining spanning 10% cut-off value. Highest (86%) when scores clustered 0 versus others. Improvement combined. Inter-observer moderate substantial whole cohort but fair group. Similarly, consensus-observer almost perfect group.ConclusionHER2-low suffers from lower among pathologists. While most cases can reproducibly be classified, small proportion remained challenging. Refining criteria consensus scoring will help select appropriate patients targeted