Evidence map›Paper›PMID 42785914›Full record

ArticleESMO open2026

HER1-HER4 expression and co-expression in advanced urothelial carcinoma.

S Coca Membribes, D M Berney, L Beltran, E Nally, F Jackson-Spence, B Szabados, S Mariathasan, T Powles, C Ackerman

Registry-linked trialAbstract read
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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. It is linked to trial NCT00949455 (A Phase II/III, Randomised, Two-Arm, Comparison of Maintenance Lapatinib Versus Placebo After First-Line Chemotherapy in Patients With HER1 and/or HER2 Overexpressing Locally Advanced or Metastatic Bladder Cancer [LaMB]), which is not on this 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.

NCT00949455 phase2 / phase3unknown statusnot on this map

A Phase II/III, Randomised, Two-Arm, Comparison of Maintenance Lapatinib Versus Placebo After First-Line Chemotherapy in Patients With HER1 and/or HER2 Overexpressing Locally Advanced or Metastatic Bladder Cancer [LaMB]

TypeinterventionalSponsorQueen Mary University of LondonRan2009Enrolled204ConditionsBladder CancerArmslapatinib ditosylate, Placebo
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
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

9 authors.

S Coca MembribesBarts Cancer Institute Biomedical Research Centre/Barts ECMC, Queen Mary University of London, London, UK.
D M BerneyDepartment of Cellular Pathology, Barts Health NHS Trust, London, UK.
L BeltranDepartment of Cellular Pathology, Royal Free London NHS Foundation Trust, London, UK.
E NallyBarts Cancer Institute Biomedical Research Centre/Barts ECMC, Queen Mary University of London, London, UK.
F Jackson-SpenceBarts Cancer Institute Biomedical Research Centre/Barts ECMC, Queen Mary University of London, London, UK.
B SzabadosBarts Cancer Institute Biomedical Research Centre/Barts ECMC, Queen Mary University of London, London, UK.
S MariathasanKite Pharma, Foster City, USA.
T PowlesBarts Cancer Institute Biomedical Research Centre/Barts ECMC, Queen Mary University of London, London, UK. Electronic address: thomas.powles1@nhs.uk.
C AckermanBarts Cancer Institute Biomedical Research Centre/Barts ECMC, Queen Mary University of London, London, UK.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe human epidermal growth factor receptor (HER) family is under evaluation as a therapeutic target in urothelial cancer (UC); the significance of expression patterns beyond those of HER2 is unclear. PATIENTS AND

methodsTumour samples from a prospective randomised phase II-III trial (NCT00949455) were analysed by immunohistochemistry (IHC) and RNA profiling. Associations with molecular subtype, chemotherapy response, and overall survival (OS) were explored. The analyses were exploratory, and P values < 0.05 were considered relevant.

resultsA total of 446 tumours were tested for HER1/HER2, 77 for HER3, and 79 for HER4 expression. HER1-HER4 were positive (IHC 1-3+) in 89%, 80%, 77%, and 75% of tumours, respectively, with high expression (IHC 3+) in 34%, 12%, 26%, and 29%. Co-expression of all four receptors occurred in 61% of tumours, with concurrent high expression in 9%. Of the tumours, 96% expressed ≥2 receptors. Luminal tumours (n = 109) showed enriched HER2 expression (93% compared with 67%, P < 0.001), and basal tumours (n = 61) showed higher enriched HER3 expression (95% compared with 77%, P = 0.02). HER1 positivity correlated with better chemotherapy responses (P = 0.02) and HER3/HER4 positivity with poorer responses (P = 0.02 and P = 0.03, respectively). No differences in OS were observed.

conclusionsHER1-HER4 are broadly and concurrently expressed in advanced UC, supporting antibody-drug conjugate development beyond HER2. Receptor expression did not correlate with OS.

Indexed as

Carcinoma, Transitional CellErbB ReceptorsReceptor, ErbB-4Urinary Bladder NeoplasmsAgedClinical Trials, Phase II as TopicClinical Trials, Phase III as TopicErb-b2 Receptor Tyrosine KinasesFemaleHumansImmunohistochemistryMaleMiddle AgedProspective StudiesRandomized Controlled Trials as TopicReceptor, ErbB-3EGFR protein, humanErb-b2 Receptor Tyrosine KinasesERBB4 protein, humanErbB ReceptorsReceptor, ErbB-3Receptor, ErbB-4ADCsEGFRHER3HER expressionurothelial carcinoma

Identifiers

PMID42785914
PMCPMC13650353

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