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Breast Cancer Research
Published in: Breast Cancer Research 1/2018

Open Access 01-12-2018 | Research article

Metformin inhibits stromal aromatase expression and tumor progression in a rodent model of postmenopausal breast cancer

Authors: Erin D. Giles, Sonali Jindal, Elizabeth A. Wellberg, Troy Schedin, Steven M. Anderson, Ann D. Thor, Dean P. Edwards, Paul S. MacLean, Pepper Schedin

Published in: Breast Cancer Research | Issue 1/2018

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Abstract

Background

Obesity and type II diabetes are linked to increased breast cancer risk in postmenopausal women. Patients treated with the antidiabetic drug metformin for diabetes or metabolic syndrome have reduced breast cancer risk, a greater pathologic complete response to neoadjuvant therapy, and improved breast cancer survival. We hypothesized that metformin may be especially effective when targeted to the menopausal transition, as this is a lifecycle window when weight gain and metabolic syndrome increase, and is also when the risk for obesity-related breast cancer increases.

Methods

Here, we used an 1-methyl-1-nitrosourea (MNU)-induced mammary tumor rat model of estrogen receptor (ER)-positive postmenopausal breast cancer to evaluate the long-term effects of metformin administration on metabolic and tumor endpoints. In this model, ovariectomy (OVX) induces rapid weight gain, and an impaired whole-body response to excess calories contributes to increased tumor glucose uptake and increased tumor proliferation. Metformin treatment was initiated in tumor-bearing animals immediately prior to OVX and maintained for the duration of the study.

Results

Metformin decreased the size of existing mammary tumors and inhibited new tumor formation without changing body weight or adiposity. Decreased lipid accumulation in the livers of metformin-treated animals supports the ability of metformin to improve overall metabolic health. We also found a decrease in the number of aromatase-positive, CD68-positive macrophages within the tumor microenvironment, suggesting that metformin targets the immune microenvironment in addition to improving whole-body metabolism.

Conclusions

These findings suggest that peri-menopause/menopause represents a unique window of time during which metformin may be highly effective in women with established, or at high risk for developing, breast cancer.
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Metadata
Title
Metformin inhibits stromal aromatase expression and tumor progression in a rodent model of postmenopausal breast cancer
Authors
Erin D. Giles
Sonali Jindal
Elizabeth A. Wellberg
Troy Schedin
Steven M. Anderson
Ann D. Thor
Dean P. Edwards
Paul S. MacLean
Pepper Schedin
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2018
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-018-0974-2

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