Evidence map›Paper›PMID 37794508›Full record

ArticleBreast cancer research : BCR2023

B-cells and regulatory T-cells in the microenvironment of HER2+ breast cancer are associated with decreased survival: a real-world analysis of women with HER2+ metastatic breast cancer.

Tessa G Steenbruggen, Denise M Wolf, Michael J Campbell, Joyce Sanders, Sten Cornelissen, Bram Thijssen, Roberto A Salgado, Christina Yau, Nick O-Grady, Amrita Basu and 8 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Breast cancer research : BCR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

11 citing papers in PubMed, 12 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

18 authors at 5 institutions in 4 countries.

Tessa G SteenbruggenDepartment of Medical Oncology, The Netherlands Cancer Institute, 1066 CX, Amsterdam, North Holland, The Netherlands. t.steenbruggen@nki.nl.
Denise M WolfDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA, 94115, USA.
Michael J CampbellDepartment of Surgery, University of California San Francisco, San Francisco, CA, 94115, USA.
Joyce SandersDepartment of Pathology, The Netherlands Cancer Institute, 1066 CX, Amsterdam, North Holland, The Netherlands.
Sten CornelissenCore Facility Molecular Pathology and Biobanking, The Netherlands Cancer Institute, 1066 CX, Amsterdam, North Holland, The Netherlands.
Bram ThijssenDepartment of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX, Amsterdam, North Holland, The Netherlands.
Roberto A SalgadoDepartment of Pathology, GZA-ZNA Hospitals, 2020, Antwerp, Belgium.
Christina YauDepartment of Surgery, University of California San Francisco, San Francisco, CA, 94115, USA.
Nick O-GradyDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA, 94115, USA.
Amrita BasuDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA, 94115, USA.
Rajith BhaskaranResearch and Development, Agendia N.V, 1043 NT, Amsterdam, North Holland, The Netherlands.
Lorenza MittempergherResearch and Development, Agendia N.V, 1043 NT, Amsterdam, North Holland, The Netherlands.
Gillian L HirstDepartment of Surgery, University of California San Francisco, San Francisco, CA, 94115, USA.
Jean-Philippe CoppeDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA, 94115, USA.
Marleen KokDepartment of Medical Oncology, The Netherlands Cancer Institute, 1066 CX, Amsterdam, North Holland, The Netherlands.
Gabe S SonkeDepartment of Medical Oncology, The Netherlands Cancer Institute, 1066 CX, Amsterdam, North Holland, The Netherlands.
Laura J van 't VeerDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA, 94115, USA.
Hugo M HorlingsDepartment of Pathology, The Netherlands Cancer Institute, 1066 CX, Amsterdam, North Holland, The Netherlands.
University of California, San Francisco · USThe Netherlands Cancer Institute · NLAgendia (Netherlands) · NLPeter MacCallum Cancer Centre · AUUniversity of Amsterdam · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDespite major improvements in treatment of HER2-positive metastatic breast cancer (MBC), only few patients achieve complete remission and remain progression free for a prolonged time. The tumor immune microenvironment plays an important role in the response to treatment in HER2-positive breast cancer and could contain valuable prognostic information. Detailed information on the cancer-immune cell interactions in HER2-positive MBC is however still lacking. By characterizing the tumor immune microenvironment in patients with HER2-positive MBC, we aimed to get a better understanding why overall survival (OS) differs so widely and which alternative treatment approaches may improve outcome.

methodsWe included all patients with HER2-positive MBC who were treated with trastuzumab-based palliative therapy in the Netherlands Cancer Institute between 2000 and 2014 and for whom pre-treatment tissue from the primary tumor or from metastases was available. Infiltrating immune cells and their spatial relationships to one another and to tumor cells were characterized by immunohistochemistry and multiplex immunofluorescence. We also evaluated immune signatures and other key pathways using next-generation RNA-sequencing data. With nine years median follow-up from initial diagnosis of MBC, we investigated the association between tumor and immune characteristics and outcome.

resultsA total of 124 patients with 147 samples were included and evaluated. The different technologies showed high correlations between each other. T-cells were less prevalent in metastases compared to primary tumors, whereas B-cells and regulatory T-cells (Tregs) were comparable between primary tumors and metastases. Stromal tumor-infiltrating lymphocytes in general were not associated with OS. The infiltration of B-cells and Tregs in the primary tumor was associated with unfavorable OS. Four signatures classifying the extracellular matrix of primary tumors showed differential survival in the population as a whole.

conclusionsIn a real-world cohort of 124 patients with HER2-positive MBC, B-cells, and Tregs in primary tumors are associated with unfavorable survival. With this paper, we provide a comprehensive insight in the tumor immune microenvironment that could guide further research into development of novel immunomodulatory strategies.

Indexed as

Breast NeoplasmsAntineoplastic Combined Chemotherapy ProtocolsErb-b2 Receptor Tyrosine KinasesFemaleHumansPrognosisT-Lymphocytes, RegulatoryTrastuzumabTumor MicroenvironmentErb-b2 Receptor Tyrosine KinasesTrastuzumabGene expressionHER2-positiveMetastatic breast cancerMultiplex immunofluorescenceSpatial compositionTumor immune microenvironment

Identifiers

PMID37794508
PMCPMC10552219
OpenAlexW4387333371

What OpenQuestion holds

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LicenceCC BY
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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.