Breast Cancer Research and Treatment

, Volume 123, Issue 2, pp 333–344 | Cite as

Dietary energy availability affects primary and metastatic breast cancer and metformin efficacy

  • Kathryn N. Phoenix
  • Frank Vumbaca
  • Melissa M. Fox
  • Rebecca Evans
  • Kevin P. ClaffeyEmail author
Preclinical study


Dietary energy restriction has been shown to repress both mammary tumorigenesis and aggressive mammary tumor growth in animal studies. Metformin, a caloric restriction mimetic, has a long history of safe use as an insulin sensitizer in diabetics and has been shown to reduce cancer incidence and cancer-related mortality in humans. To determine the potential impact of dietary energy availability and metformin therapy on aggressive breast tumor growth and metastasis, an orthotopic syngeneic model using triple negative 66cl4 tumor cells in Balb/c mice was employed. The effect of dietary restriction, a standard maintenance diet or a diet with high levels of free sugar, were tested for their effects on tumor growth and secondary metastases to the lung. Metformin therapy with the various diets indicated that metformin can be highly effective at suppressing systemic metabolic biomarkers such as IGF-1, insulin and glucose, especially in the high energy diet treated animals. Long-term metformin treatment demonstrated moderate yet significant effects on primary tumor growth, most significantly in conjunction with the high energy diet. When compared to the control diet, the high energy diet promoted tumor growth, expression of the inflammatory adipokines leptin and resistin, induced lung priming by bone marrow-derived myeloid cells and promoted metastatic potential. Metformin had no effect on adipokine expression or the development of lung metastases with the standard or the high energy diet. These data indicate that metformin may have tumor suppressing activity where a metabolic phenotype of high fuel intake, metabolic syndrome, and diabetes exist, but may have little or no effect on events controlling the metastatic niche driven by proinflammatory events.


Breast cancer Dietary energy restriction Metformin Metastasis Leptin Resistin 



The authors would like to thank Nancy Ryan and Xiaoxiao Hong for their technical assistance. This work was supported by NIH:NCI CA064436 and the Connecticut Breast Health Initiative, Inc.

Supplementary material

10549_2009_647_MOESM1_ESM.pdf (63 kb)
(PDF 63 kb)


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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Kathryn N. Phoenix
    • 1
  • Frank Vumbaca
    • 1
  • Melissa M. Fox
    • 1
  • Rebecca Evans
    • 1
  • Kevin P. Claffey
    • 1
    Email author
  1. 1.Center for Vascular Biology, Department of Cell BiologyUniversity of Connecticut Health CenterFarmingtonUSA

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