Evidence map›Paper›PMID 38321542›Full record

ArticleBreast cancer research : BCR2024

Prognostic impact of HER2 biomarker levels in trastuzumab-treated early HER2-positive breast cancer.

Caroline Rönnlund, Emmanouil G Sifakis, Caroline Schagerholm, Qiao Yang, Emelie Karlsson, Xinsong Chen, Theodoros Foukakis, Jodi Weidler, Michael Bates, Irma Fredriksson and 2 more

Open access · goldAbstract read
In one paragraph

Article in Breast cancer research : BCR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
1.7field-weighted citation impact, top 14% 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

2 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
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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

12 authors at 2 institutions in 1 country.

Caroline RönnlundDepartment of Oncology and Pathology, Karolinska Institutet, Visionsgatan 56, CCK R8:04, 17176, Stockholm, Sweden. caroline.ronnlund@ki.se.
Emmanouil G SifakisDepartment of Oncology and Pathology, Karolinska Institutet, Visionsgatan 56, CCK R8:04, 17176, Stockholm, Sweden.
Caroline SchagerholmDepartment of Oncology and Pathology, Karolinska Institutet, Visionsgatan 56, CCK R8:04, 17176, Stockholm, Sweden.
Qiao YangDepartment of Oncology and Pathology, Karolinska Institutet, Visionsgatan 56, CCK R8:04, 17176, Stockholm, Sweden.
Emelie KarlssonDepartment of Oncology and Pathology, Karolinska Institutet, Visionsgatan 56, CCK R8:04, 17176, Stockholm, Sweden.
Xinsong ChenDepartment of Oncology and Pathology, Karolinska Institutet, Visionsgatan 56, CCK R8:04, 17176, Stockholm, Sweden.
Theodoros FoukakisDepartment of Oncology and Pathology, Karolinska Institutet, Visionsgatan 56, CCK R8:04, 17176, Stockholm, Sweden.
Jodi WeidlerMedical and Scientific Affairs and Strategy, Oncology, Cepheid, Sunnyvale, CA, USA.
Michael BatesMedical and Scientific Affairs and Strategy, Oncology, Cepheid, Sunnyvale, CA, USA.
Irma FredrikssonDepartment of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Stephanie Robertson *Department of Oncology and Pathology, Karolinska Institutet, Visionsgatan 56, CCK R8:04, 17176, Stockholm, Sweden.
Johan Hartman *Department of Oncology and Pathology, Karolinska Institutet, Visionsgatan 56, CCK R8:04, 17176, Stockholm, Sweden.
Karolinska Institutet · SEKarolinska University Hospital · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundOverexpression of human epidermal growth factor receptor 2 (HER2) caused by HER2 gene amplification is a driver in breast cancer tumorigenesis. We aimed to investigate the prognostic significance of manual scoring and digital image analysis (DIA) algorithm assessment of HER2 copy numbers and HER2/CEP17 ratios, along with ERBB2 mRNA levels among early-stage HER2-positive breast cancer patients treated with trastuzumab.

methodsThis retrospective study comprised 371 early HER2-positive breast cancer patients treated with adjuvant trastuzumab, with HER2 re-testing performed on whole tumor sections. Digitized tumor tissue slides were manually scored and assessed with uPath HER2 Dual ISH image analysis, breast algorithm. Targeted ERBB2 mRNA levels were assessed by the Xpert® Breast Cancer STRAT4 Assay. HER2 copy number and HER2/CEP17 ratio from in situ hybridization assessment, along with ERBB2 mRNA levels, were explored in relation to recurrence-free survival (RFS).

resultsThe analysis showed that patients with tumors with the highest and lowest manually counted HER2 copy number levels had worse RFS than those with intermediate levels (HR = 2.7, CI 1.4-5.3, p = 0.003 and HR = 2.1, CI 1.1-3.9, p = 0.03, respectively). A similar trend was observed for HER2/CEP17 ratio, and the DIA algorithm confirmed the results. Moreover, patients with tumors with the highest and the lowest values of ERBB2 mRNA had a significantly worse prognosis (HR = 2.7, CI 1.4-5.1, p = 0.003 and HR = 2.8, CI 1.4-5.5, p = 0.004, respectively) compared to those with intermediate levels.

conclusionsOur findings suggest that the association between any of the three HER2 biomarkers and RFS was nonlinear. Patients with tumors with the highest levels of HER2 gene amplification or ERBB2 mRNA were associated with a worse prognosis than those with intermediate levels, which is of importance to investigate in future clinical trials studying HER2-targeted therapy.

Indexed as

Breast NeoplasmsErb-b2 Receptor Tyrosine KinasesFemaleHumansPrognosisRetrospective StudiesRNA, MessengerTrastuzumabERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesRNA, MessengerTrastuzumabBreast cancerDigital image analysisERBB2 mRNAHER2Prognosis

Identifiers

PMID38321542
PMCPMC10848443
OpenAlexW4391609285

What OpenQuestion holds

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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.