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Effects of metformin on transcriptomic and metabolomic profiles in breast cancer survivors enrolled in the randomized placebo-controlled MetBreCS trial
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Effects of metformin on transcriptomic and metabolomic profiles in breast cancer survivors enrolled in the randomized placebo-controlled MetBreCS trial
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Journal Article
Effects of metformin on transcriptomic and metabolomic profiles in breast cancer survivors enrolled in the randomized placebo-controlled MetBreCS trial
2025
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Aged
/ Breast Neoplasms - drug therapy
/ Breast Neoplasms - metabolism
/ Cancer
/ Diabetes mellitus (non-insulin dependent)
/ Estrone
/ Female
/ Gene Expression Regulation, Neoplastic - drug effects
/ Humanities and Social Sciences
/ Humans
/ Hypoglycemic Agents - pharmacology
/ Hypoglycemic Agents - therapeutic use
/ Placebos
/ Science
/ Steroids
/ Tissues
