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; Islam M. Miligy; Cecily M. Quinn; Elena Provenzano; Abeer M. Shaaban; Caterina Marchiò; Michael S. Toss; Grace Gallagy; Ciara Murray; Janice Walshe; Ayaka Katayama; Karim Eldib; Nahla Badr; Bruce Tanchel; Rebecca Millican-Slater; Colin Purdie; Dave Purnell; Sarah E. Pinder; Ian O. Ellis; Andrew H. S. Lee

doi:10.1038/s41416-021-01351-8

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 (Lead / Corresponding author), Islam M. Miligy, Cecily M. Quinn, Elena Provenzano, Abeer M. Shaaban, Caterina Marchiò, Michael S. Toss, Grace Gallagy, Ciara Murray, Janice Walshe, Ayaka Katayama, Karim Eldib, Nahla Badr, Bruce Tanchel, Rebecca Millican-Slater, Colin Purdie, Dave Purnell, Sarah E. Pinder, Ian O. Ellis, Andrew H. S. Lee

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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.

Original language	English
Pages (from-to)	1836-1842
Number of pages	7
Journal	British Journal of Cancer
Volume	124
Early online date	24 Mar 2021
DOIs	https://doi.org/10.1038/s41416-021-01351-8
Publication status	Published - 25 May 2021

Keywords

Breast cancer

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Rakha, E. A., Miligy, I. M., Quinn, C. M., Provenzano, E., Shaaban, A. M., Marchiò, C., Toss, M. S., Gallagy, G., Murray, C., Walshe, J., Katayama, A., Eldib, K., Badr, N., Tanchel, B., Millican-Slater, R., Purdie, C., Purnell, D., Pinder, S. E., Ellis, I. O., & Lee, A. H. S. (2021). 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. British Journal of Cancer, 124, 1836-1842. https://doi.org/10.1038/s41416-021-01351-8

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title = "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",

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.",

keywords = "Breast cancer",

author = "Rakha, {Emad A.} and Miligy, {Islam M.} and Quinn, {Cecily M.} and Elena Provenzano and Shaaban, {Abeer M.} and Caterina Marchi{\`o} and Toss, {Michael S.} and Grace Gallagy and Ciara Murray and Janice Walshe and Ayaka Katayama and Karim Eldib and Nahla Badr and Bruce Tanchel and Rebecca Millican-Slater and Colin Purdie and Dave Purnell and Pinder, {Sarah E.} and Ellis, {Ian O.} and Lee, {Andrew H. S.}",

note = "Funding Information: We acknowledge all those who contributed to the collection of cases. We thank Nottingham Health Science Biobank and PathLAKE project for supporting this study. CaM is supported by AIRC under IG 2019—ID 22850 project. A.M.S. is supported by Birmingham Cancer Research UK Centre (C17422/A25154). Publisher Copyright: {\textcopyright} 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = may,

day = "25",

doi = "10.1038/s41416-021-01351-8",

language = "English",

volume = "124",

pages = "1836--1842",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "Springer Nature",

}

Rakha, EA, Miligy, IM, Quinn, CM, Provenzano, E, Shaaban, AM, Marchiò, C, Toss, MS, Gallagy, G, Murray, C, Walshe, J, Katayama, A, Eldib, K, Badr, N, Tanchel, B, Millican-Slater, R, Purdie, C, Purnell, D, Pinder, SE, Ellis, IO & Lee, AHS 2021, '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', British Journal of Cancer, vol. 124, pp. 1836-1842. https://doi.org/10.1038/s41416-021-01351-8

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. / Rakha, Emad A. (Lead / Corresponding author); Miligy, Islam M.; Quinn, Cecily M. et al.
In: British Journal of Cancer, Vol. 124, 25.05.2021, p. 1836-1842.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - 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

AU - Rakha, Emad A.

AU - Miligy, Islam M.

AU - Quinn, Cecily M.

AU - Provenzano, Elena

AU - Shaaban, Abeer M.

AU - Marchiò, Caterina

AU - Toss, Michael S.

AU - Gallagy, Grace

AU - Murray, Ciara

AU - Walshe, Janice

AU - Katayama, Ayaka

AU - Eldib, Karim

AU - Badr, Nahla

AU - Tanchel, Bruce

AU - Millican-Slater, Rebecca

AU - Purdie, Colin

AU - Purnell, Dave

AU - Pinder, Sarah E.

AU - Ellis, Ian O.

AU - Lee, Andrew H. S.

N1 - Funding Information: We acknowledge all those who contributed to the collection of cases. We thank Nottingham Health Science Biobank and PathLAKE project for supporting this study. CaM is supported by AIRC under IG 2019—ID 22850 project. A.M.S. is supported by Birmingham Cancer Research UK Centre (C17422/A25154). Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/5/25

Y1 - 2021/5/25

N2 - 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.

AB - 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.

KW - Breast cancer

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U2 - 10.1038/s41416-021-01351-8

DO - 10.1038/s41416-021-01351-8

M3 - Article

C2 - 33762723

SN - 0007-0920

VL - 124

SP - 1836

EP - 1842

JO - British Journal of Cancer

JF - British Journal of Cancer

ER -

Rakha EA, Miligy IM, Quinn CM, Provenzano E, Shaaban AM, Marchiò C et al. 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. British Journal of Cancer. 2021 May 25;124:1836-1842. Epub 2021 Mar 24. doi: 10.1038/s41416-021-01351-8