Evidence map›Paper›PMID 41261233›Full record

ArticleEMBO molecular medicine2026

Activated glucocorticoid receptor is an estrogen receptor silencer in ER+ metastatic breast cancer.

Madhuri Manivannan, Charly Jehanno, Michal Kloc, Jorge Gomez Miragaya, Maren Diepenbruck, Katrin Volkmann, Marie-May Coissieux, Marta Palafox, Adelin Rouchon, Nicolas Kramer and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EMBO molecular medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–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

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Review
  4. 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

20 authors.

Madhuri ManivannanDepartment of Biomedicine, University of Basel, University Hospital Basel, Basel, Switzerland.ORCID http://orcid.org/0009-0000-9156-9793
Charly JehannoDepartment of Biomedicine, University of Basel, University Hospital Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0002-2897-6027
Michal KlocDepartment of Biomedicine, University of Basel, University Hospital Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0002-4575-7723
Jorge Gomez MiragayaDepartment of Biomedicine, University of Basel, University Hospital Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0003-1801-4681
Maren DiepenbruckDepartment of Biomedicine, University of Basel, University Hospital Basel, Basel, Switzerland.
Katrin VolkmannDepartment of Biomedicine, University of Basel, University Hospital Basel, Basel, Switzerland.
Marie-May CoissieuxDepartment of Biomedicine, University of Basel, University Hospital Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0001-5017-5253
Marta PalafoxDepartment of Biomedicine, University of Basel, University Hospital Basel, Basel, Switzerland.
Adelin RouchonDepartment of Biomedicine, University of Basel, University Hospital Basel, Basel, Switzerland.
Nicolas KramerDepartment of Biomedicine, University of Basel, University Hospital Basel, Basel, Switzerland.
Alexander SchmidtProteomics Core Facility, Biozentrum, University of Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0002-3149-2381
Yannick BlumDepartment of Biomedicine, University of Basel, University Hospital Basel, Basel, Switzerland.
Baptiste HamelinDepartment of Biomedicine, University of Basel, University Hospital Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0001-8928-8597
Helen SchusterInstitute of Pathology and Medical Genetics, University Hospital Basel, University of Basel, Basel, Switzerland.ORCID http://orcid.org/0009-0008-3824-3434
Martin HeidingerDepartment of Biomedicine, University of Basel, University Hospital Basel, Basel, Switzerland.
Simone MuenstInstitute of Pathology and Medical Genetics, University Hospital Basel, University of Basel, Basel, Switzerland.
Marcus VetterCancer Centre Baselland, Medical University Clinic, Cantonal Hospital Baselland, Liestal, Switzerland.ORCID http://orcid.org/0009-0004-1003-1078
Christian KurzederDepartment of Gynecology, University Hospital Basel, University of Basel, Basel, Switzerland.
Walter P WeberDepartment of Surgery, University Hospital Basel, Basel, Switzerland.
Mohamed Bentires-AljDepartment of Biomedicine, University of Basel, University Hospital Basel, Basel, Switzerland. m.bentires-alj@unibas.ch.ORCID http://orcid.org/0000-0001-6344-1127

Funding

EC | ERC | HORIZON EUROPE European Research Council (ERC) 694033 STEM-BCPCEC | H2020 | PRIORITY 'Excellent science' | H2020 Marie Skłodowska-Curie Actions (MSCA) 841872 EpicanKrebsliga Beider Basel (Cancer League of Basel-City and Basel-Country) KFS-4414-02-2018Krebsliga Beider Basel (Cancer League of Basel-City and Basel-Country) KLbB-5572-02-2022Universität Basel (UB) 3MM1062
6 · The paper itself

Abstract

Estrogen Receptor alpha (ER)-positive, HER2-negative breast cancers are less aggressive than other subtypes and show good patient clinical outcome because they are likely to respond to endocrine therapies. Unfortunately, therapy-resistant metastases may develop and start an inexorable downhill course. ESR1 mutations leading to resistance to endocrine therapy are prevalent in 20-55% of patients with ER+ metastatic breast cancer. Here, we found that glucocorticoid receptor (GR) activation by dexamethasone in ESR1 mutant metastases-bearing mice decreases liver metastases and prolongs survival. Transcriptomic and proteomic profiling revealed that GR activation not only downregulates estrogen response signature but also induces dramatic loss of ER itself. ChIP-Seq analyses show that prolonged dexamethasone treatment almost completely abrogates ER chromatin binding and that GR binds a subset of ER-related genes, including ESR1. Finally, the GR activity signature predicts a good outcome in patients with ER+ breast cancer. In summary, we show that dexamethasone inhibits ER+ metastatic growth by depleting ER, and hence could be tested for treating patients with ER+ metastatic breast cancer, particularly those suffering from refractory ESR1 mutant metastases.

Indexed as

Breast NeoplasmsEstrogen Receptor alphaReceptors, GlucocorticoidAnimalsCell Line, TumorDexamethasoneDisease Models, AnimalFemaleGene Expression ProfilingHumansLiver NeoplasmsMiceNeoplasm MetastasisSurvival AnalysisDexamethasoneESR1 protein, humanEstrogen Receptor alphaReceptors, GlucocorticoidBreast CancerERGRMetastasisSteroid Nuclear Receptors

Identifiers

PMID41261233
PMCPMC12808765

What OpenQuestion holds

Textmetadata
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.