Effects of metformin on transcriptomic and metabolomic profiles in breast cancer survivors enrolled in the randomized placebo-controlled MetBreCS trial
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 bre...
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Nature Portfolio
2025-05-01
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| Online Access: | https://doi.org/10.1038/s41598-025-01705-9 |
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| author | 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 Dorothy D. Sears Bernardo Bonanni Sara Gandini Harriet Johansson Gunnar Mellgren |
| author_facet | 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 Dorothy D. Sears Bernardo Bonanni Sara Gandini Harriet Johansson Gunnar Mellgren |
| author_sort | Pouda Panahandeh Strømland |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-25dc3ce1653e4e7c8d6fc1bcf9f16c14 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-25dc3ce1653e4e7c8d6fc1bcf9f16c142025-08-20T01:51:30ZengNature PortfolioScientific Reports2045-23222025-05-0115111310.1038/s41598-025-01705-9Effects of metformin on transcriptomic and metabolomic profiles in breast cancer survivors enrolled in the randomized placebo-controlled MetBreCS trialPouda Panahandeh Strømland0Bjørn-Erik Bertelsen1Kristin Viste2Anastasia Chrysovalantou Chatziioannou3Federica Bellerba4Nivonirina Robinot5Amarine Trolat6Marianne Hauglid Flågeng7Augustin Scalbert8Pekka Keski-Rahkonen9Dorothy D. Sears10Bernardo Bonanni11Sara Gandini12Harriet Johansson13Gunnar Mellgren14Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University HospitalHormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University HospitalHormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University HospitalInternational Agency for Research on Cancer, Nutrition and Metabolism BranchDepartment of Experimental Oncology, IEO, European Institute of Oncology IRCCSInternational Agency for Research on Cancer, Nutrition and Metabolism BranchInternational Agency for Research on Cancer, Nutrition and Metabolism BranchHormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University HospitalInternational Agency for Research on Cancer, Nutrition and Metabolism BranchInternational Agency for Research on Cancer, Nutrition and Metabolism BranchCollege of Health Solutions, Arizona State UniversityDivision of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCSDepartment of Experimental Oncology, IEO, European Institute of Oncology IRCCSDivision of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCSHormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University HospitalAbstract 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.https://doi.org/10.1038/s41598-025-01705-9MetforminBreast cancer recurrenceSex steroid hormones17β-estradiolEstroneMetabolomics |
| spellingShingle | 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 Dorothy D. Sears Bernardo Bonanni Sara Gandini Harriet Johansson Gunnar Mellgren Effects of metformin on transcriptomic and metabolomic profiles in breast cancer survivors enrolled in the randomized placebo-controlled MetBreCS trial Scientific Reports Metformin Breast cancer recurrence Sex steroid hormones 17β-estradiol Estrone Metabolomics |
| title | Effects of metformin on transcriptomic and metabolomic profiles in breast cancer survivors enrolled in the randomized placebo-controlled MetBreCS trial |
| title_full | Effects of metformin on transcriptomic and metabolomic profiles in breast cancer survivors enrolled in the randomized placebo-controlled MetBreCS trial |
| title_fullStr | Effects of metformin on transcriptomic and metabolomic profiles in breast cancer survivors enrolled in the randomized placebo-controlled MetBreCS trial |
| title_full_unstemmed | Effects of metformin on transcriptomic and metabolomic profiles in breast cancer survivors enrolled in the randomized placebo-controlled MetBreCS trial |
| title_short | Effects of metformin on transcriptomic and metabolomic profiles in breast cancer survivors enrolled in the randomized placebo-controlled MetBreCS trial |
| title_sort | effects of metformin on transcriptomic and metabolomic profiles in breast cancer survivors enrolled in the randomized placebo controlled metbrecs trial |
| topic | Metformin Breast cancer recurrence Sex steroid hormones 17β-estradiol Estrone Metabolomics |
| url | https://doi.org/10.1038/s41598-025-01705-9 |
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