Evidence map›Paper›PMID 42296698›Full record

ArticleESMO open2026

ERBB2/HER2 landscape and prognostic impact: large-scale, real-world analysis across solid cancers.

A Shreenivas, A Elliott, T Corbiere, H-Z Chen, B George, M Kamgar, S Chakrabarti, A Desai, D Bracken-Clarke, E Xue and 7 more

Abstract read
In one paragraph

Article in ESMO open, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

17 authors.

A ShreenivasDepartment Oncology, Froedtert Hospital & Medical College of Wisconsin, Milwaukee, USA; City of Hope National Medical Center, Duarte, USA. Electronic address: ashreenivas@coh.org.
A ElliottClinical and Translational Research, Caris Life Sciences - Headquarters, Irving, USA.
T CorbiereMedical Affairs Department, Caris Life Sciences - Arizona Office, Phoenix, USA.
H-Z ChenDepartment Oncology, Froedtert Hospital & Medical College of Wisconsin, Milwaukee, USA.
B GeorgeDepartment Oncology, Froedtert Hospital & Medical College of Wisconsin, Milwaukee, USA.
M KamgarDepartment Oncology, Froedtert Hospital & Medical College of Wisconsin, Milwaukee, USA.
S ChakrabartiMedical Oncology Department, University Hospitals Seidman Cancer Center, Cleveland, USA.
A DesaiDivision of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, USA.
D Bracken-ClarkeCenter for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, USA.
E XueCenter for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, USA.
C S FloudasCenter for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, USA.
J ThomasDepartment of Oncology, USC - University of Southern California - Norris Comprehensive Cancer Center, Los Angeles, USA.
J XiuClinical and Translational Research, Caris Life Sciences - Lab & Specimen Receiving, Phoenix, USA.
G SledgeClinical and Translational Research, Caris Life Sciences - Lab & Specimen Receiving, Phoenix, USA.
E S AntonarakisDivision of Hematology, Oncology and Transplantation, Department of Medicine, Masonic Cancer Center - University of Minnesota, Minneapolis, USA.
Y BoumberDivision of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, USA.
R KurzrockDepartment Oncology, Froedtert Hospital & Medical College of Wisconsin, Milwaukee, USA; WIN Consortium, Chevilly-Larue, France; Department of Oncology, University of Nebraska, Omaha, USA. Electronic address: rkurzrock@mcw.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundWe evaluated the frequency and prognostic impact of human epidermal growth factor receptor 2 (HER2) protein expression [immunohistochemistry (IHC)] and correlations with ERBB2 genomic alterations in a large database of molecularly profiled real-world patients (Caris Life Sciences, Phoenix, AZ). MATERIALS AND

methodsWe analyzed 206 750 tumors for ERBB2 copy number alterations and pathogenic mutations (using next-generation sequencing) and 88 530 samples for HER2 IHC data (stratified as 0, 1+, 2+, or 3+). RNA (whole transcriptome) was also evaluated. Overall survival (OS) was based on real-world insurance claims.

resultsERBB2 amplifications and/or mutations were found in a subset of multiple cancer types. ERBB2 amplifications were often but not always associated with higher HER2 IHC expression. ERBB2 pathogenic mutations and ERBB2 amplifications correlated significantly across cancers and in some cancer subtypes. Statistically significant associations with HER2 IHC positivity were also identified in a subgroup of tumors exhibiting mutations, even without amplifications. ERBB2 transcripts were markedly increased among HER2 IHC 3+ tumors. Median OS for HER2 (3+, 2+, 1+, and 0+) tumors were 30.6, 26.9, 26.5, and 23 months, respectively [hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.77-0.83; HR 0.89, 95% CI 0.87-0.91; and HR 0.90, 95% CI 0.88-0.92, respectively (P < 0.001)]. However, survival advantages observed in the overall cohort appeared largely driven by breast and gastric cancers for which HER2-targeted therapies are available.

conclusionComplex relationships between ERBB2 alterations and HER2 IHC expression exist, including increased expression in non-ERBB2-amplified tumors with pathogenic mutations. Importantly, ERBB2/HER2 amplification and/or mutation rates as well as transcript and protein expression varied between cancers and within cancer types, emphasizing the need for individual assessment.

Indexed as

Biomarkers, TumorErb-b2 Receptor Tyrosine KinasesNeoplasmsFemaleGene AmplificationHumansImmunohistochemistryMaleMutationPrognosisBiomarkers, TumorERBB2 protein, humanErb-b2 Receptor Tyrosine KinasescancerERBB2genomicsHER2immunohistochemistryRNA

Identifiers

PMID42296698
PMCPMC13285824

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.