Evidence mapPaperPMID 40374694Full record

Trial reportScientific reports2025

Effects of metformin on transcriptomic and metabolomic profiles in breast cancer survivors enrolled in the randomized placebo-controlled MetBreCS trial.

Pouda Panahandeh Strømland, Bjørn-Erik Bertelsen, Kristin Viste, Anastasia Chrysovalantou Chatziioannou, Federica Bellerba, Nivonirina Robinot, Amarine Trolat, Marianne Hauglid Flågeng, Augustin Scalbert, Pekka Keski-Rahkonen and 5 more

Abstract readRandomized Controlled TrialClinical Trial, Phase II
In one paragraph

Trial report in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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.

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. Review
  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

15 authors.

Pouda Panahandeh StrømlandHormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway.
Bjørn-Erik BertelsenHormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway.
Kristin VisteHormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway.
Anastasia Chrysovalantou ChatziioannouInternational Agency for Research on Cancer, Nutrition and Metabolism Branch, Lyon, France.
Federica BellerbaDepartment of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy.
Nivonirina RobinotInternational Agency for Research on Cancer, Nutrition and Metabolism Branch, Lyon, France.
Amarine TrolatInternational Agency for Research on Cancer, Nutrition and Metabolism Branch, Lyon, France.
Marianne Hauglid FlågengHormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway.
Augustin ScalbertInternational Agency for Research on Cancer, Nutrition and Metabolism Branch, Lyon, France.
Pekka Keski-RahkonenInternational Agency for Research on Cancer, Nutrition and Metabolism Branch, Lyon, France.
Dorothy D SearsCollege of Health Solutions, Arizona State University, Phoenix, AZ, USA.
Bernardo BonanniDivision of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, Milan, Italy.
Sara GandiniDepartment of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy.
Harriet JohanssonDivision of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, Milan, Italy.
Gunnar MellgrenHormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway. gunnar.mellgren@uib.no.

Funding

World Health Organization 001
6 · The paper itself

Abstract

Metformin reduces the incidence of breast cancer in patients with obesity and type 2 diabetes. However, our knowledge of the effects of metformin on breast cancer recurrence is limited. Within the randomized double-blind placebo-controlled phase II trial MetBreCS, we examined changes in breast tissue from breast cancer survivors with BMI > 25 kg/m2 after treatment with metformin. To identify metformin-regulated signaling pathways, we integrated the transcriptomic, metabolomic and steroid hormone profiles using bivariate and functional analyses. We identified MS4A1, HBA2, MT-RNR1, MT-RNR2, EGFL6 and FDCSP expression to be differentially expressed in breast tissues from metformin-treated postmenopausal women. The integration of transcriptomic and metabolomic profiles revealed down-regulation of immune response genes associated with reduced levels of arginine and citrulline in the metformin-treated group. The integration of transcriptomic and steroid hormone profiles showed an enrichment of steroid hormone biosynthesis and metabolism pathways with highly negatively correlated CYP11A1 and CYP1B1 expression in breast tissue from postmenopausal metformin-treated women. Our results indicate that postmenopausal breast cancer survivors treated with metformin have specific changes in breast tissue gene expression that may prevent the development of new tumors.Trial registration: MetBreCs trial is registered at European Union Clinical Trials Register (EudraCT Protocol # 2015-001001-14) on 07/10/2015.

Indexed as

Breast NeoplasmsHypoglycemic AgentsMetabolomeMetforminTranscriptomeAgedCancer SurvivorsDouble-Blind MethodFemaleGene Expression Regulation, NeoplasticHumansMetabolomicsMiddle AgedPostmenopauseHypoglycemic AgentsMetformin17β-estradiolBreast cancer recurrenceEstroneMetabolomicsMetforminSex steroid hormones

Identifiers

PMID40374694
PMCPMC12081705

What Socratic 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 Socratic graph.