Selecting patients with HER2-low breast cancer: Getting out of the tangle

Ximena Baez-Navarro; Roberto Salgado; Carsten Denkert; Jochen K. Lennerz; Frédérique Penault-Llorca; Giuseppe Viale; John M.S. Bartlett; Carolien H.M. van Deurzen

doi:10.1016/j.ejca.2022.08.022

Selecting patients with HER2-low breast cancer: Getting out of the tangle

Ximena Baez-Navarro^*
, Roberto Salgado
, Carsten Denkert
, Jochen K. Lennerz
, Frédérique Penault-Llorca
, Giuseppe Viale
, John M.S. Bartlett
, Carolien H.M. van Deurzen

^*Corresponding author for this work

Pathology

Antwerp
Peter Maccallum Cancer Centre
University Hospital Marburg
Massachusetts General Hospital
Université Clermont Auvergne
University of Milan
University of Edinburgh

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

35 Citations (Scopus)

86 Downloads (Pure)

Abstract

The promising effect of antibody–drug conjugates on breast cancer with low expression of HER2 (HER2-low) raises many questions regarding the optimal selection of patients for this treatment. A key question is whether HER2 immunohistochemistry, an assay optimised to detect HER2 amplification, is reliable enough to assess HER2 protein levels to select patients with HER2-low breast cancer in daily pathology practices worldwide. Moreover, whether this assessment can be performed with sufficient reproducibility between pathologists in daily practices is debatable. Herein, we address the historical track record of the CAP-ASCO HER2 Guidelines, the reported limited reproducibility by pathologists of HER2 immunohistochemistry in the non-amplified cases, and the performance variation of different antibodies. Based on this summary, we propose solutions to improve the robustness to enable reliable identification of patients with HER2-low breast cancer.

Original language	English
Pages (from-to)	187-192
Number of pages	6
Journal	European Journal of Cancer
Volume	175
DOIs	https://doi.org/10.1016/j.ejca.2022.08.022
Publication status	Published - Nov 2022

Bibliographical note

Funding Information:
CvD received funding from AstraZeneca. The funder had no role in the design or writing of this manuscript.JB reports consultancies from Insight Genetics, Inc. BioNTech AG Biotheranostics, Inc. Pfizer, Rna Diagnostics Inc., oncoXchange/MedcomXchange Communications Inc. Herbert Smith French Solicitors and OncoCyte Corporation. He is involved in a scientific advisory board of MedcomXchange Communications Inc. He received honoraria from NanoString Technologies, Inc. Oncology Education, Biotheranostics, Inc, MedcomXchange Communications Inc. and research funding from Thermo Fisher Scientific Genoptix, Agendia, NanoString Technologies, Inc. Stratifyer GmbH Biotheranostics, Inc. Travel, accommodation expenses were received from Biotheranostics, Inc., NanoString Technologies, Inc, and the Breast Cancer Society of Canada. He reports the following patents: 1) CIN4 predicts benefit from anthracycline, National Phase Application, (Canada, Jan. 11, 2017), 2) Systems, Devices and Methods for Constructing and Using a Biomarker, National Phase Application, 15/328,108 (United States, Jan. 23, 2017); 15824751.0 (Europe, Jan. 12, 2017); (Canada, Jan. 12, 2017), 3) Targeting the Histone Pathway to Detect and Overcome Anthracycline Resistance (IP Title), National Phase Application, PCT/CA2016/000247, Patent Application #: 3000858 (Country of filing: Canada – Patent Application Date: Apr. 4, 2018) and 4) Immune Gene Signature Predicts Anthracycline Benefit, PCT (international application), PCT/CA2016/000305, Filing date: Dec. 7, 2016.FPL reports personal fees from Astrazeneca, BMS, Daiichy-Sankyo, MSD, Roche, Seagen, Diaceutics, Veracyte, research support from Astrazeneca, Daiichy Sankyo, Roche, MSD and BMS.GV reports personal fees from AstraZeneca, BMS, Daiichy-Sankyo, MSD, Roche, Seagen, Pfizer, and research support from AstraZeneca and Roche.RS is supported by the Breast Cancer Research Foundation (BCRF, grant nr. 17-194).

Funding Information:
RS is supported by the Breast Cancer Research Foundation (BCRF, grant nr. 17-194 ).

Publisher Copyright:
© 2022 The Author(s)

UN SDGs

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

SDG 3 Good Health and Well-being

Access to Document

10.1016/j.ejca.2022.08.022Licence: CC BY

PIIS0959804922005093Final published version, 752 KBLicence: CC BY

Cite this

@article{dadee019e41f4849b26867902347860e,

title = "Selecting patients with HER2-low breast cancer: Getting out of the tangle",

abstract = "The promising effect of antibody{\textendash}drug conjugates on breast cancer with low expression of HER2 (HER2-low) raises many questions regarding the optimal selection of patients for this treatment. A key question is whether HER2 immunohistochemistry, an assay optimised to detect HER2 amplification, is reliable enough to assess HER2 protein levels to select patients with HER2-low breast cancer in daily pathology practices worldwide. Moreover, whether this assessment can be performed with sufficient reproducibility between pathologists in daily practices is debatable. Herein, we address the historical track record of the CAP-ASCO HER2 Guidelines, the reported limited reproducibility by pathologists of HER2 immunohistochemistry in the non-amplified cases, and the performance variation of different antibodies. Based on this summary, we propose solutions to improve the robustness to enable reliable identification of patients with HER2-low breast cancer.",

author = "Ximena Baez-Navarro and Roberto Salgado and Carsten Denkert and Lennerz, \{Jochen K.\} and Fr{\'e}d{\'e}rique Penault-Llorca and Giuseppe Viale and Bartlett, \{John M.S.\} and \{van Deurzen\}, \{Carolien H.M.\}",

note = "Funding Information: CvD received funding from AstraZeneca. The funder had no role in the design or writing of this manuscript.JB reports consultancies from Insight Genetics, Inc. BioNTech AG Biotheranostics, Inc. Pfizer, Rna Diagnostics Inc., oncoXchange/MedcomXchange Communications Inc. Herbert Smith French Solicitors and OncoCyte Corporation. He is involved in a scientific advisory board of MedcomXchange Communications Inc. He received honoraria from NanoString Technologies, Inc. Oncology Education, Biotheranostics, Inc, MedcomXchange Communications Inc. and research funding from Thermo Fisher Scientific Genoptix, Agendia, NanoString Technologies, Inc. Stratifyer GmbH Biotheranostics, Inc. Travel, accommodation expenses were received from Biotheranostics, Inc., NanoString Technologies, Inc, and the Breast Cancer Society of Canada. He reports the following patents: 1) CIN4 predicts benefit from anthracycline, National Phase Application, (Canada, Jan. 11, 2017), 2) Systems, Devices and Methods for Constructing and Using a Biomarker, National Phase Application, 15/328,108 (United States, Jan. 23, 2017); 15824751.0 (Europe, Jan. 12, 2017); (Canada, Jan. 12, 2017), 3) Targeting the Histone Pathway to Detect and Overcome Anthracycline Resistance (IP Title), National Phase Application, PCT/CA2016/000247, Patent Application \#: 3000858 (Country of filing: Canada {\textendash} Patent Application Date: Apr. 4, 2018) and 4) Immune Gene Signature Predicts Anthracycline Benefit, PCT (international application), PCT/CA2016/000305, Filing date: Dec. 7, 2016.FPL reports personal fees from Astrazeneca, BMS, Daiichy-Sankyo, MSD, Roche, Seagen, Diaceutics, Veracyte, research support from Astrazeneca, Daiichy Sankyo, Roche, MSD and BMS.GV reports personal fees from AstraZeneca, BMS, Daiichy-Sankyo, MSD, Roche, Seagen, Pfizer, and research support from AstraZeneca and Roche.RS is supported by the Breast Cancer Research Foundation (BCRF, grant nr. 17-194). Funding Information: RS is supported by the Breast Cancer Research Foundation (BCRF, grant nr. 17-194 ). Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = nov,

doi = "10.1016/j.ejca.2022.08.022",

language = "English",

volume = "175",

pages = "187--192",

journal = "European Journal of Cancer",

issn = "0959-8049",

publisher = "Elsevier Ltd.",

}

TY - JOUR

T1 - Selecting patients with HER2-low breast cancer

T2 - Getting out of the tangle

AU - Baez-Navarro, Ximena

AU - Salgado, Roberto

AU - Denkert, Carsten

AU - Lennerz, Jochen K.

AU - Penault-Llorca, Frédérique

AU - Viale, Giuseppe

AU - Bartlett, John M.S.

AU - van Deurzen, Carolien H.M.

N1 - Funding Information: CvD received funding from AstraZeneca. The funder had no role in the design or writing of this manuscript.JB reports consultancies from Insight Genetics, Inc. BioNTech AG Biotheranostics, Inc. Pfizer, Rna Diagnostics Inc., oncoXchange/MedcomXchange Communications Inc. Herbert Smith French Solicitors and OncoCyte Corporation. He is involved in a scientific advisory board of MedcomXchange Communications Inc. He received honoraria from NanoString Technologies, Inc. Oncology Education, Biotheranostics, Inc, MedcomXchange Communications Inc. and research funding from Thermo Fisher Scientific Genoptix, Agendia, NanoString Technologies, Inc. Stratifyer GmbH Biotheranostics, Inc. Travel, accommodation expenses were received from Biotheranostics, Inc., NanoString Technologies, Inc, and the Breast Cancer Society of Canada. He reports the following patents: 1) CIN4 predicts benefit from anthracycline, National Phase Application, (Canada, Jan. 11, 2017), 2) Systems, Devices and Methods for Constructing and Using a Biomarker, National Phase Application, 15/328,108 (United States, Jan. 23, 2017); 15824751.0 (Europe, Jan. 12, 2017); (Canada, Jan. 12, 2017), 3) Targeting the Histone Pathway to Detect and Overcome Anthracycline Resistance (IP Title), National Phase Application, PCT/CA2016/000247, Patent Application #: 3000858 (Country of filing: Canada – Patent Application Date: Apr. 4, 2018) and 4) Immune Gene Signature Predicts Anthracycline Benefit, PCT (international application), PCT/CA2016/000305, Filing date: Dec. 7, 2016.FPL reports personal fees from Astrazeneca, BMS, Daiichy-Sankyo, MSD, Roche, Seagen, Diaceutics, Veracyte, research support from Astrazeneca, Daiichy Sankyo, Roche, MSD and BMS.GV reports personal fees from AstraZeneca, BMS, Daiichy-Sankyo, MSD, Roche, Seagen, Pfizer, and research support from AstraZeneca and Roche.RS is supported by the Breast Cancer Research Foundation (BCRF, grant nr. 17-194). Funding Information: RS is supported by the Breast Cancer Research Foundation (BCRF, grant nr. 17-194 ). Publisher Copyright: © 2022 The Author(s)

PY - 2022/11

Y1 - 2022/11

N2 - The promising effect of antibody–drug conjugates on breast cancer with low expression of HER2 (HER2-low) raises many questions regarding the optimal selection of patients for this treatment. A key question is whether HER2 immunohistochemistry, an assay optimised to detect HER2 amplification, is reliable enough to assess HER2 protein levels to select patients with HER2-low breast cancer in daily pathology practices worldwide. Moreover, whether this assessment can be performed with sufficient reproducibility between pathologists in daily practices is debatable. Herein, we address the historical track record of the CAP-ASCO HER2 Guidelines, the reported limited reproducibility by pathologists of HER2 immunohistochemistry in the non-amplified cases, and the performance variation of different antibodies. Based on this summary, we propose solutions to improve the robustness to enable reliable identification of patients with HER2-low breast cancer.

AB - The promising effect of antibody–drug conjugates on breast cancer with low expression of HER2 (HER2-low) raises many questions regarding the optimal selection of patients for this treatment. A key question is whether HER2 immunohistochemistry, an assay optimised to detect HER2 amplification, is reliable enough to assess HER2 protein levels to select patients with HER2-low breast cancer in daily pathology practices worldwide. Moreover, whether this assessment can be performed with sufficient reproducibility between pathologists in daily practices is debatable. Herein, we address the historical track record of the CAP-ASCO HER2 Guidelines, the reported limited reproducibility by pathologists of HER2 immunohistochemistry in the non-amplified cases, and the performance variation of different antibodies. Based on this summary, we propose solutions to improve the robustness to enable reliable identification of patients with HER2-low breast cancer.

UR - https://www.scopus.com/pages/publications/85138154004

U2 - 10.1016/j.ejca.2022.08.022

DO - 10.1016/j.ejca.2022.08.022

M3 - Article

C2 - 36137393

AN - SCOPUS:85138154004

SN - 0959-8049

VL - 175

SP - 187

EP - 192

JO - European Journal of Cancer

JF - European Journal of Cancer

ER -

Selecting patients with HER2-low breast cancer: Getting out of the tangle

Abstract

Bibliographical note

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this