Evidence map›Paper›PMID 40195456›Full record

ReviewNature reviews. Clinical oncology2025

HER2 testing: evolution and update for a companion diagnostic assay.

Charles J Robbins, Katherine M Bates, David L Rimm

Abstract readReview
In one paragraph

Review in Nature reviews. Clinical oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed.

  1. A modular framework for antibody-drug conjugate biomarkers.Nature reviews. Clinical oncology · 2026
    Review
  2. Article
  3. Review
  4. Article
  5. Redefining breast cancer: therapeutic opportunities in HER2-low and emerging molecular subtypes.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Repurposing HER2 IHC: Pan-HER2 and Low-HER2.Applied immunohistochemistry & molecular morphology : AIMM · 2026
    Review
  11. Review
  12. Article
  13. Article
  14. Review
  15. Review
  16. Predictive Biomarkers of Antibody-Drug Conjugate Efficacy for Solid Tumors: Current Challenges and the Potential Role of Quantitative Proteomics.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Review
  17. Review
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors.

Charles J Robbins *Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-3130-7107
Katherine M Bates *Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0001-8956-6331
David L RimmDepartment of Pathology, Yale University School of Medicine, New Haven, CT, USA. david.rimm@yale.edu.ORCID http://orcid.org/0000-0001-5820-4397

Funding

Yale Pathology Tissue Services Shared ResourceP30CA016359 · NCI · YALE UNIVERSITY · PI Eric P. Winer · 1985 to 2026
$85.0M
Next-generation diagnostic approaches for HER2-low breast cancer and trastuzumab deruxtecan therapyF30CA287869 · NCI · YALE UNIVERSITY · PI Charles John Robbins · 2024 to 2026
$124k
NCI NIH HHS F30 CA287869NCI NIH HHS P30 CA016359
6 · The paper itself

Abstract

Human epidermal growth factor receptor 2 (HER2; encoded by ERBB2) testing has been a cornerstone of patient selection for HER2-targeted therapies, principally in breast cancer but also in several other solid tumours. Since the introduction of HercepTest as the original companion diagnostic for trastuzumab, HER2 assessment methods have evolved substantially, incorporating various testing modalities, from western blots, immunohistochemistry and fluorescence in situ hybridization, to early chromogenic quantitative methods and, probably in the future, fully quantitative methods. The advent of highly effective HER2-targeted antibody-drug conjugates with clinical activity at low levels of HER2 expression, such as trastuzumab deruxtecan, has necessitated the re-evaluation of HER2 testing, particularly for HER2-low tumours. In this Review, we provide an in-depth overview of the evolution of HER2 testing, the current clinical guidelines for HER2 testing across various solid tumours, challenges associated with current testing methodologies and the emerging potential of quantitative techniques. We discuss the importance of accurately defining HER2-low expression for therapeutic decision-making and how newer diagnostic approaches, such as quantitative immunofluorescence and RNA-based assays, might address the limitations of traditional immunohistochemistry-based methods. As the use of HER2-targeted therapies continues to expand to a wider range of tumour types, ensuring the precision and accuracy of HER2 testing will be crucial for guiding treatment strategies and improving patient outcomes.

Indexed as

Biomarkers, TumorBreast NeoplasmsErb-b2 Receptor Tyrosine KinasesNeoplasmsFemaleHumansImmunohistochemistryIn Situ Hybridization, FluorescenceMolecular Targeted TherapyTrastuzumabBiomarkers, TumorERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesTrastuzumab

Identifiers

PMID40195456
PMCPMC12903097

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.