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Metformin may protect nondiabetic breast cancer women from metastasis

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Abstract

Metformin, a widely prescribed oral hypoglycemic agent, has recently received a big interest because of its potential antitumorigenic effects in different cancer types. The present study investigated the impact of adding metformin to breast cancer adjuvant therapy in nondiabetic women on, insulin like growth factor-1 (IGF-1), IGF binding protein-3 (IGFBP-3), insulin, fasting blood glucose (FBG), the molar ratio of IGF-1 to IGFBP-3, homeostatic model assessment of insulin resistance (HOMA-IR) and metastasis. 102 women with newly diagnosed breast cancer were divided into 2 main groups, a control group and a metformin group. All women were treated with adjuvant therapy, according to the protocols of Ministry of Health and Population and National Cancer Institute, Egypt. Moreover, the women in the metformin group received 850 mg of metformin twice daily. Blood samples were collected at baseline, after chemotherapy (CT), after 6 months of hormonal therapy (6-HT) and 12 months of hormonal therapy (12-HT) for analysis of serum IGF-1, IGFBP-3, insulin, FBG and cancer antigen 15-3 (CA15-3). Metformin resulted in a significant reduction of IGF-1, IGF-1: IGFBP-3 molar ratio, insulin, FBG and HOMA-IR. On the other hand, metformin caused a significant increase of IGFBP-3. Moreover, metformin significantly decreased the numbers of metastatic cases after 6-HT. Metformin may have potential antitumor and antimetastatic effects that need further clinical investigations. This may be attributed to either the significant increase of the apoptotic inducer IGFBP-3 or/and the significant reduction of mitogenic insulin, IGF-1, free bioactive IGF-1, FBG and HOMA-IR.

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Abbreviations

IGF-1:

Insulin like growth factor-1

IGFBP-3:

IGF binding protein-3

HOMA:

Homeostatic model assessment

HOMA-IR:

HOMA of insulin resistance

CA15-3:

Cancer antigen 15-3

FBG:

Fasting blood glucose

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Correspondence to Noha Ahmed El-Bassiouny.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of College of Pharmacy, Tanta university ethical committee, Damnhour Oncology Center ethical committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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EL-Haggar, S.M., El-Shitany, N.A., Mostafa, M.F. et al. Metformin may protect nondiabetic breast cancer women from metastasis. Clin Exp Metastasis 33, 339–357 (2016). https://doi.org/10.1007/s10585-016-9782-1

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