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
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,
Abeer M. Shaaban
Affiliations
Mohamed Zaakouk
Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK; Cancer Pathology, National Cancer Institute, Cairo University, Cairo, Egypt
Cecily Quinn
Department of Histopathology, St Vincent's University Hospital, Elm Park, Ireland; UCD School of Medicine, Dublin, Ireland
Elena Provenzano
Addenbrookes Hospital and NIHR Cambridge Biomedical Research Centre, Cambridge, UK; Department of Histopathology, Addenbrookes Hospital, Cambridge, UK
Clinton Boyd
Histopathology, Belfast Health and Social Care Trust, Belfast, UK
Grace Callagy
Discipline of Pathology, University of Galway, School of Medicine, Lambe Institute for Translational Research, Galway, Ireland
Soha Elsheikh
Department of Cellular Pathology, Royal Free Hospital, London, UK; Research Department of Pathology, University College London, Cancer Institute, London, UK
Joe Flint
Birmingham Tissue Analytics, University of Birmingham, UK
Rebecca Millican-Slater
Department of Cellular Pathology, St James's University Hospital, Leeds, UK
Anu Gunavardhan
Department of Histopathology, Glan Clwyd Hospital Betsi Cadwaladr University Health Board, Bodelwyddan, UK
Yasmeen Mir
Pathology, Liverpool University Hospitals Foundation Trust, Liverpool, UK
Purnima Makhija
Pathology, Barts Health NHS Trust, London, UK
Silvana Di Palma
Cellular Pathology Department, Royal Surrey Hospital NHS Foundation Trust, Guildford, UK
Susan Pritchard
Pathology, Wythenshawe Hospital Manchester Foundation Trust, Manchester, UK
Bruce Tanchel
Cellular Pathology, Heart of England NHS Foundation Trust, Birmingham, UK
Emad Rakha
Histopathology Department, Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, UK
Nehal M. Atallah
Histopathology Department, Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, UK; Department of Pathology, Faculty of Medicine, Menoufia University, Egypt
Andrew H.S. Lee
Histopathology Department, Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, UK
Sarah Pinder
School of Cancer & Pharmaceutical Sciences, Kings College London, London, UK
Abeer M. Shaaban
Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK; Cellular Pathology, Queen Elizabeth Hospital Birmingham, Birmingham, UK; Corresponding author. Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK
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.
