HER2-low breast cancers: challenges in the interpretation of immunohistochemistry

Noel Chia; Mihir Ananta Gudi; Emad Rakha; Puay Hoon Tan

doi:10.4103/singaporemedj.SMJ-2023-037

HER2-low breast cancers: challenges in the interpretation of immunohistochemistry

Singapore Med J. 2024 Mar 13. doi: 10.4103/singaporemedj.SMJ-2023-037. Online ahead of print.

Authors

Noel Chia¹, Mihir Ananta Gudi², Emad Rakha³, Puay Hoon Tan^{2

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Affiliations

¹ Department of Pathology, National University Hospital, Singapore.
² Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, Singapore.
³ Department of Pathology, School of Medicine, University of Nottingham and Nottingham University Hospitals NHS Trust, United Kingdom.
⁴ Luma Medical Centre, Royal Square Medical Centre, Singapore.
⁵ Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
⁶ Department of Pathology, University of Western Sydney, Sydney, Australia.

PMID: 38478736
DOI: 10.4103/singaporemedj.SMJ-2023-037

Abstract

Overexpression of human epidermal growth factor receptor 2 (HER2) protein in breast cancers carries significant prognostic and therapeutic implications. Anti-HER2 blockade has shown to be a useful adjunct to surgery in treating HER2-positive tumours. Up till today, the HER2 immunohistochemistry (IHC) and in situ hybridisation (ISH) scoring algorithms are geared towards identifying HER2-positive cases. A recently published Phase III clinical trial (DESTINY-Breast04) has demonstrated that an antibody-drug conjugate (trastuzumab-deruxtecan) significantly reduced disease progression and death in patients with metastatic disease with IHC score 1+ or 2+ and without ISH amplification, defining a new category of cases known as HER2 low. At present, IHC scores 0, 1+ and 2+ show significant interobserver variability, and identifying HER2-low breast cancers may pose significant challenges with the current algorithms. More work is needed in this area to better define HER2-low breast cancers, target the appropriate group of patients and assess treatment efficacy.