Retrospective observational study of HER2 immunohistochemistry in borderline breast cancer patients undergoing neoadjuvant therapy, with an emphasis on Group 2 (HER2/CEP17 ratio ≥2.0, HER2 copy number <4.0 signals/cell) cases

Emad A Rakha^{1

2

3}, Islam M Miligy^{4

5}, Cecily M Quinn⁶, Elena Provenzano⁷, Abeer M Shaaban⁸, Caterina Marchiò^{9

10}, Michael S Toss⁴, Grace Gallagy¹¹, Ciara Murray⁶, Janice Walshe⁶, Ayaka Katayama⁴, Karim Eldib¹², Nahla Badr⁸, Bruce Tanchel⁸, Rebecca Millican-Slater¹³, Colin Purdie¹⁴, Dave Purnell¹⁵, Sarah E Pinder¹⁶, Ian O Ellis^{12

4}, Andrew H S Lee¹²

Affiliations

¹ Department of Histopathology, Nottingham University Hospitals, Nottingham, UK. emad.rakha@nottingham.ac.uk.
² Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, Nottingham City Hospital, The University of Nottingham, Nottingham, UK. emad.rakha@nottingham.ac.uk.
³ Histopathology Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Egypt. emad.rakha@nottingham.ac.uk.
⁴ Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, Nottingham City Hospital, The University of Nottingham, Nottingham, UK.
⁵ Histopathology Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Egypt.
⁶ Histopathology, Breast Check, Irish National Breast Screening Programme and St. Vincent's University Hospital, Dublin, Ireland.
⁷ Department of Pathology, University of Cambridge, Cambridge, UK.
⁸ Queen Elizabeth Hospital Birmingham and Institute of Cancer and Genomic Sciences, The University of Birmingham, Birmingham, UK.
⁹ Department of Medical Sciences, University of Turin, Turin, Italy.
¹⁰ Pathology Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy.
¹¹ Discipline of Pathology, School of Medicine, Lambe Institute for Translational Research, National University of Ireland, Galway, Ireland.
¹² Department of Histopathology, Nottingham University Hospitals, Nottingham, UK.
¹³ Department of Histopathology, St James's University Hospital, Leeds, UK.
¹⁴ Department of Breast Pathology, Ninewells Hospital and Medical School, Dundee, UK.
¹⁵ Histopathology Department, University Hospitals of Leicester, Leicester, UK.
¹⁶ Division of Cancer Studies, King's College London, Guy's Hospital, London, UK.

PMID: 33762723
PMCID: PMC8144199
DOI: 10.1038/s41416-021-01351-8

Observational Study

Retrospective observational study of HER2 immunohistochemistry in borderline breast cancer patients undergoing neoadjuvant therapy, with an emphasis on Group 2 (HER2/CEP17 ratio ≥2.0, HER2 copy number <4.0 signals/cell) cases

Emad A Rakha et al. Br J Cancer. 2021 May.

. 2021 May;124(11):1836-1842.

doi: 10.1038/s41416-021-01351-8. Epub 2021 Mar 24.

Authors

Affiliations

¹ Department of Histopathology, Nottingham University Hospitals, Nottingham, UK. emad.rakha@nottingham.ac.uk.
² Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, Nottingham City Hospital, The University of Nottingham, Nottingham, UK. emad.rakha@nottingham.ac.uk.
³ Histopathology Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Egypt. emad.rakha@nottingham.ac.uk.
⁴ Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, Nottingham City Hospital, The University of Nottingham, Nottingham, UK.
⁵ Histopathology Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Egypt.
⁶ Histopathology, Breast Check, Irish National Breast Screening Programme and St. Vincent's University Hospital, Dublin, Ireland.
⁷ Department of Pathology, University of Cambridge, Cambridge, UK.
⁸ Queen Elizabeth Hospital Birmingham and Institute of Cancer and Genomic Sciences, The University of Birmingham, Birmingham, UK.
⁹ Department of Medical Sciences, University of Turin, Turin, Italy.
¹⁰ Pathology Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy.
¹¹ Discipline of Pathology, School of Medicine, Lambe Institute for Translational Research, National University of Ireland, Galway, Ireland.
¹² Department of Histopathology, Nottingham University Hospitals, Nottingham, UK.
¹³ Department of Histopathology, St James's University Hospital, Leeds, UK.
¹⁴ Department of Breast Pathology, Ninewells Hospital and Medical School, Dundee, UK.
¹⁵ Histopathology Department, University Hospitals of Leicester, Leicester, UK.
¹⁶ Division of Cancer Studies, King's College London, Guy's Hospital, London, UK.

PMID: 33762723
PMCID: PMC8144199
DOI: 10.1038/s41416-021-01351-8

Abstract

Background: The ASCO/CAP guidance on HER2 testing in breast cancer (BC) has recently changed. Group 2 tumours with immunohistochemistry score 2+ and HER2/CEP17 ratio ≥2.0 and HER2 copy number <4.0 signals/cell were re-classified as HER2 negative. This study aims to examine the response of Group 2 tumours to neoadjuvant chemotherapy (NACT).

Methods: 749 BC cases were identified from 11 institutions. The association between HER2 groups and pathological complete response (pCR) was assessed.

Results: 54% of immunohistochemistry HER2 positive (score 3+) BCs showed pCR, compared to 19% of immunohistochemistry 2+ FISH amplified cases. 27% of Group 2 treated with HER2 targeted therapy achieved pCR, compared to 19 and 11% in the combined Groups 1 + 3 and Groups 4 + 5, respectively. No difference in pCR rates was identified between Group 2 and Group 1 or combined Groups 1 + 3. However, Group 2 response rate was higher than Groups 4 + 5 (p = 0.017).

Conclusion: No difference in pCR was detected in tumours with a HER2/CEP17 ratio ≥2.0 and a HER2 score 2+ by IHC when stratified by HER2 gene copy number. Our data suggest that ASCO/CAP HER2 Group 2 carcinomas should be evaluated further with respect to eligibility for HER2 targeted therapy.

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Conflict of interest statement

The authors declare no competing interests.

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Retrospective observational study of HER2 immunohistochemistry in borderline breast cancer patients undergoing neoadjuvant therapy, with an emphasis on Group 2 (HER2/CEP17 ratio ≥2.0, HER2 copy number <4.0 signals/cell) cases

Affiliations

Retrospective observational study of HER2 immunohistochemistry in borderline breast cancer patients undergoing neoadjuvant therapy, with an emphasis on Group 2 (HER2/CEP17 ratio ≥2.0, HER2 copy number <4.0 signals/cell) cases

Authors

Affiliations

Abstract

Conflict of interest statement

References

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LinkOut - more resources

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Medical

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