Evidence map›Paper›PMID 36030496›Full record

ArticleHistopathology2022

Refining the definition of HER2-low class in invasive breast cancer.

Nehal M Atallah, Michael S Toss, Andrew R Green, Nigel P Mongan, Graham Ball, Emad A Rakha

Open access · hybridAbstract read
In one paragraph

Article in Histopathology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.8field-weighted citation impact, top 7% of its field
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

16 citing papers in PubMed, 27 citations in OpenAlex.

  1. Observational
  2. Article
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Bispecific antibody drug conjugates: Making 1+1>2.Acta pharmaceutica Sinica. B · 2024
    Review
  10. Challenges in HER2-low breast cancer identification, detection, and treatment.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2024
    Review
  11. Article
  12. Evaluation ofCancers · 2023
    Article
  13. Article
  14. HER2-low breast cancer: insights on pathological testing.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2023
    Review
  15. Review
  16. 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

6 authors at 3 institutions in 2 countries.

Nehal M AtallahDepartment of Histopathology, School of Medicine, the University of Nottingham and Nottingham University, Hospitals NHS Trust, Nottingham, UK.ORCID https://orcid.org/0000-0001-6845-5608
Michael S TossDivision of Cancer and Stem Cells, Biodiscovery Institute, School of Medicine, University of Nottingham, Nottingham, UK.
Andrew R GreenDivision of Cancer and Stem Cells, Biodiscovery Institute, School of Medicine, University of Nottingham, Nottingham, UK.
Nigel P MonganSchool of Veterinary Medicine and Sciences, University of Nottingham, Sutton Bonington, UK.
Graham BallDivision of Life Sciences, Nottingham Trent University, Nottingham, UK.
Emad A RakhaDepartment of Histopathology, School of Medicine, the University of Nottingham and Nottingham University, Hospitals NHS Trust, Nottingham, UK.ORCID https://orcid.org/0000-0002-5009-5525
University of Nottingham · GBNottingham University Hospitals NHS Trust · GBNottingham Trent University · GB

Funding

Egyptian Ministry of Higher EducationUK GovernmentUK Research and Innovation
6 · The paper itself

Abstract

backgroundEmerging evidence indicates that breast cancer (BC) patients whose tumours express HER2 protein without HER2 gene amplification (HER2-low), can benefit from antibody-drug conjugates (ADC). However, the current definition of HER2-low BC remains incomplete with low rates of concordance. This study aims to refine HER2-low definition with emphasis on distinguishing HER2 score 0 from score 1+ to identify patients who are eligible for ADC.

methodsA BC cohort (n = 363) with HER2 IHC scores 0, 1+ and 2+ (without HER2 gene amplification) and available HER2 mRNA was included. HER2 staining intensity, pattern and subcellular localisation were reassessed. Artificial neural network analysis was applied to cluster the cohort and to distinguish HER2 score 0 from 1+. Reproducibility and reliability of the refined criteria were tested.

resultsHER2 IHC score 1+ was refined as membranous staining in invasive cells as either: (1) faint intensity in ≥ 20% of cells regardless the circumferential completeness, (2) weak complete staining in ≤ 10%, (3) weak incomplete staining in > 10% and (4) moderate incomplete staining in ≤ 10%. Based on this, 63% of the HER2-negative cases were reclassified as positive (HER2-low). The refined score showed perfect observer agreement compared to the moderate agreement in the original clinical scores. Similar results were generated when the refined score was applied on the independent BC cohorts. A proposal to refine the definition of other HER2 classes is presented.

conclusionThis study refined the definition of HER2-low BC based on correlation with HER2 mRNA and distinguished between HER2 IHC score 1+ and score 0 tumours.

Indexed as

Breast NeoplasmsImmunoconjugatesErb-b2 Receptor Tyrosine KinasesFemaleHumansImmunohistochemistryIn Situ Hybridization, FluorescenceReproducibility of ResultsRNA, MessengerErb-b2 Receptor Tyrosine KinasesImmunoconjugatesRNA, MessengerANNbreast cancerHER2 lowHER2 mRNArefining

Identifiers

PMID36030496
PMCPMC9826019
OpenAlexW4293388046

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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.