ArticleJournal of translational medicine2022
Metabolomic profiles of metformin in breast cancer survivors: a pooled analysis of plasmas from two randomized placebo-controlled trials.
Article in Journal of translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01302379 (Obesity-related Mechanisms and Mortality in Breast Cancer Survivors), which is not on this map. Cited by 12 papers.
What it found
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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.
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.
Obesity-related Mechanisms and Mortality in Breast Cancer Survivors
Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Effects of metformin on transcriptomic and metabolomic profiles in breast cancer survivors enrolled in the randomized placebo-controlled MetBreCS trial.Scientific reports · 2025Trial
- Effect of metformin and lifestyle intervention on adipokines and hormones in breast cancer survivors: a pooled analysis from two randomized controlled trials.Breast cancer research and treatment · 2024Trial
- Senescent obesity signature in breast cancer: a paradigm of reverse cardio-oncology.European heart journal · 2026Review
- Salivary metabolic profile landscape for gastric cancer screening: a metabolomic approach.Cancer cell international · 2025Article
- The Utility of Metabolomics in Spinal Cord Injury: Opportunities for Biomarker Discovery and Neuroprotection.International journal of molecular sciences · 2025Review
- Article
- Development and characterisation of a novel 3D in vitro model of obesity-associated breast cancer as a tool for drug testing.NPJ breast cancer · 2025Article
- Unveiling the atlas of associations between 1,400 plasma metabolites and 24 tumors: Mendelian randomization analyses.Translational cancer research · 2024Article
- A Multiomics, Molecular Atlas of Breast Cancer Survivors.Metabolites · 2024Article
- Metformin: From Diabetes to Cancer-Unveiling Molecular Mechanisms and Therapeutic Strategies.Biology · 2024Review
- Metformin and Breast Cancer: Current Findings and Future Perspectives from Preclinical and Clinical Studies.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundObesity is a major health concern for breast cancer survivors, being associated with high recurrence and reduced efficacy during cancer treatment. Metformin treatment is associated with reduced breast cancer incidence, recurrence and mortality. To better understand the underlying mechanisms through which metformin may reduce recurrence, we aimed to conduct metabolic profiling of overweight/obese breast cancer survivors before and after metformin treatment.
methodsFasting plasma samples from 373 overweight or obese breast cancer survivors randomly assigned to metformin (n = 194) or placebo (n = 179) administration were collected at baseline, after 6 months (Reach For Health trial), and after 12 months (MetBreCS trial). Archival samples were concurrently analyzed using three complementary methods: untargeted LC-QTOF-MS metabolomics, targeted LC-MS metabolomics (AbsoluteIDQ p180, Biocrates), and gas chromatography phospholipid fatty acid assay. Multivariable linear regression models and family-wise error correction were used to identify metabolites that significantly changed after metformin treatment.
resultsParticipants (n = 352) with both baseline and study end point samples available were included in the analysis. After adjusting for confounders such as study center, age, body mass index and false discovery rate, we found that metformin treatment was significantly associated with decreased levels of citrulline, arginine, tyrosine, caffeine, paraxanthine, and theophylline, and increased levels of leucine, isoleucine, proline, 3-methyl-2-oxovalerate, 4-methyl-2-oxovalerate, alanine and indoxyl-sulphate. Long-chain unsaturated phosphatidylcholines (PC ae C36:4, PC ae C38:5, PC ae C36:5 and PC ae C38:6) were significantly decreased with the metformin treatment, as were phospholipid-derived long-chain n-6 fatty acids. The metabolomic profiles of metformin treatment suggest change in specific biochemical pathways known to impair cancer cell growth including activation of CYP1A2, alterations in fatty acid desaturase activity, and altered metabolism of specific amino acids, including impaired branched chain amino acid catabolism.
conclusionsOur results in overweight breast cancer survivors identify new metabolic effects of metformin treatment that may mechanistically contribute to reduced risk of recurrence in this population and reduced obesity-related cancer risk reported in observational studies.
trial registrationClinicalTrials.gov identifier: NCT01302379 and EudraCT Protocol #: 2015-001001-14.
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Registered trials
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.