Proposal to distinguish HER2-low from HER2-normal breast cancer by in situ hybridisation

Yen Ying Chen, Ching Fen Yang, Chih Y. Hsu

Research output: Contribution to journalArticlepeer-review


Aims: € HER2-low' breast cancer is an emerging issue as the clinical trials for anti-HER2 antibody-drug conjugates (trastuzumab deruxtecan) are making progress. A reliable method to identify HER2-low cancers is needed. This study aimed to evaluate immunohistochemistry (IHC) and in situ hybridisation (ISH) in detecting HER2-low status. Methods: We evaluated the HER2 ISH data grouped by the IHC consensus in proficiency tests (PTs), and compared the HER2 ISH results between HER2 IHC scored 0 (IHC-0) and IHC scored 1+ (IHC-1+) tumours from in-house tissue microarrays (TMAs). Since benign/normal glands have HER2 expression and ideally should not be affected by targeted therapy, we evaluated HER2 ISH results in peritumoural benign glands of 52 breast cancers as reference values. Results: None of the 565 tissue cores in PTs achieved an 80% participant agreement of IHC-1+. In PTs and in-house TMAs, HER2 signals of the IHC-1+cores (median: 2.6 and 2.0, respectively) were significantly higher than those of IHC-0 cores (median: 2.0 and 1.7, respectively). But the ranges of HER2 signals had a considerable overlap between IHC-1+and IHC-0 cores. The HER2 signals and HER2:CEP17 ratios of peritumoural benign glands exhibited normal distributions, and their upper bounds of the 95% reference intervals were 2.10 and 1.30, respectively. Conclusions: Current HER2 testing algorithms are unsatisfactory in detecting HER2-low cases. Using ISH to detect tumour with HER2 signals and HER2:CEP17 ratio higher than the upper bound of the benign glands can be an alternative method.

Original languageEnglish
Article number208444
Pages (from-to)753-756
Number of pages4
JournalJournal of Clinical Pathology
Issue number11
Publication statusAccepted/In press - 2022


  • Breast Neoplasms
  • Genes, erbB-2
  • In Situ Hybridization
  • Staining and Labeling

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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