Evidence map›Paper›PMID 24706169›Full record

ArticleBreast cancer research and treatment2014

HER2/HER3 heterodimers and p21 expression are capable of predicting adjuvant trastuzumab response in HER2+ breast cancer.

Andrew R Green, Fabrício F T Barros, Tarek M A Abdel-Fatah, Paul Moseley, Christopher C Nolan, Alice C Durham, Emad A Rakha, Stephen Chan, Ian O Ellis

Open access · hybridAbstract read
In one paragraph

Article in Breast cancer research and treatment, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 12% 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

26 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.

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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 at 3 institutions in 1 country.

Andrew R GreenMolecular Pathology Research Unit, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham City Hospital, Nottingham, NG5 1PB, UK, andrew.green@nottingham.ac.uk.
Fabrício F T Barros
Tarek M A Abdel-Fatah
Paul Moseley
Christopher C Nolan
Alice C Durham
Emad A Rakha
Stephen Chan
Ian O Ellis
Nottingham University Hospitals NHS Trust · GBUniversity of Nottingham · GBNottingham City Hospital · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Human epidermal growth factor receptor 2 (HER2) plays an important role in breast cancer progression and provides predictive information for response to targeted therapy including trastuzumab although this is limited. Downstream pathways, such as PI3K/Akt, are associated with HER2/HER3 heterodimerization promoting survival and proliferation amongst cancer cells. Thus, patient outcome and trastuzumab therapy effectiveness might be further characterised by HER2/HER3 dimerisation and its signalling pathways. HER2/HER3 dimerisation status was assessed, using chromogenic in situ Proximity Ligation Assay, in two breast cancer series: early stage primary breast cancer, including 224 HER2+ patients that were not submitted to trastuzumab, and HER2+ breast cancer where patients were treated with adjuvant trastuzumab (n = 143). Levels of biomarkers including PI3K, pAKT, ER, PgR, HER3, BCL2, p53, PTEN and p21 were measured using immunohistochemistry. Levels of HER2/HER3 heterodimers were compared with biomarker expression and patient outcome. An association between high levels of HER2/HER3 dimerisation and absence of hormone receptors, ER and PgR, was observed. We further show for the first time the presence of HER2/HER3 heterodimers and the loss of p21 expression in HER2+ breast cancer predicts a significantly poorer outcome when submitted to adjuvant trastuzumab. Breast cancer patients that reveal high levels of HER2/HER3 dimerisation and loss of p21 are associated with poor survival prognosis in patients with HER2+ breast cancer treated with adjuvant trastuzumab. Further quantification analysis of HER dimer/ligand complexes and downstream signalling pathways will begin to unravel the complex associations with patient outcome and its relationship with sensitivity to targeted treatment.

Indexed as

Protein MultimerizationAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBiomarkers, TumorBreast NeoplasmsChemotherapy, AdjuvantCyclin-Dependent Kinase Inhibitor p21Drug Resistance, NeoplasmErb-b2 Receptor Tyrosine KinasesFemaleHumansImmunohistochemistryIn Situ HybridizationKaplan-Meier EstimateMiddle AgedReceptor, ErbB-3Antibodies, Monoclonal, HumanizedAntineoplastic AgentsBiomarkers, TumorCDKN1A protein, humanCyclin-Dependent Kinase Inhibitor p21ERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesERBB3 protein, humanReceptor, ErbB-3Trastuzumab

Identifiers

PMID24706169
PMCPMC3984415
OpenAlexW2031018710

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.