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. 2022 Nov:175:187-192.
doi: 10.1016/j.ejca.2022.08.022. Epub 2022 Sep 19.

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

Ximena Baez-Navarro  1 , Roberto Salgado  2 , Carsten Denkert  3 , Jochen K Lennerz  4 , Frédérique Penault-Llorca  5 , Giuseppe Viale  6 , John M S Bartlett  7 , Carolien H M van Deurzen  8
Affiliations
Free article

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

Ximena Baez-Navarro et al. Eur J Cancer. 2022 Nov.
Free article

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.

Keywords: Biomarker; Breast cancer; HER2-low; Immunohistochemistry; Trastuzumab-deruxtecan.

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Conflict of interest statement

Conflict of interest statement CvD received funding from AstraZeneca. The funder had no role in the design or writing of this manuscript. RS reports non-financial support from Merck and Bristol Myers Squibb (BMS), research support from Merck, Puma Biotechnology and Roche, and personal fees from Roche, BMS and Exact Sciences for advisory boards. 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. All remaining authors have declared no conflicts of interest.

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