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Proposal to distinguish HER2-low from HER2-normal breast cancer by in situ hybridisation
  1. Yen-Ying Chen1,2,3,
  2. Ching-Fen Yang3,4,
  3. Chih-Yi Hsu3,4,5
  1. 1Department of Pathology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan
  2. 2Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
  3. 3School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
  4. 4Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
  5. 5College of Nursing, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan
  1. Correspondence to Dr Chih-Yi Hsu, Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; cyhsu{at}vghtpe.gov.tw

Abstract

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.

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

Data availability statement

All data relevant to the study are included in the article or uploaded as supplemental information. Data are available in online supplemental table.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplemental information. Data are available in online supplemental table.

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Footnotes

  • Handling editor Cheok Soon Lee.

  • Contributors Conceptualisation and design: Y-YC, C-FY, C-YH. Data acquisition, analysis and interpretation: Y-YC and C-YH. Manuscript preparation, editing and approval: Y-YC, C-FY and C-YH. Manuscript guarantor: C-YH.

  • Funding This work was partly supported by grants from Taipei Veterans General Hospital (V111C-200) and National Science and Technology Council, Taiwan (NSTC 111-2320-B-075-003-).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.