The effect of metformin on biomarkers associated with breast cancer outcomes: a systematic review, meta-analysis, and dose–response of randomized clinical trials

Rahmani, Jamal; Manzari, Nicla; Thompson, Jacqueline; Gudi, Sai Krishna; Chhabra, Manik; Naik, Gurudatta; Mousavi, Seyed Mohammad; Varkaneh, Hamed Kord; Clark, Cain C. T.; Zhang, Yong

doi:10.1007/s12094-019-02108-9

Cited by 33 publications

(24 citation statements)

References 54 publications

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“…Moreover, women using metformin in combination with other anti-hyperglycemic drugs reportedly showed a lower risk of breast cancer occurrence, although not significant, when compared to women using metformin alone [223]. While metformin notably inhibits cell growth and proliferation-related pathways, these effects may be in part related to the ability of metformin to reduce insulin resistance, insulin levels, and circulating levels of glucose [65]. However, it remains largely unknown if non-diabetic women with breast cancer, or non-diabetic individuals with other forms of cancer, would benefit from taking metformin [149].…”

Section: Efficacy In Non-diabetic Patients and Non-diabetic Cancer Pamentioning

confidence: 98%

“…There are two general mechanisms that could explain the putative anti-cancer effects of metformin. The 'indirect' anti-cancer effects of metformin arise from its ability to reduce insulin resistance, insulin levels, and fasting glucose levels [65]. Physiologically, insulin and insulin-like growth factor-1 (IGF1) largely regulate carbohydrate and lipid metabolism and storage and protein synthesis via transmembrane receptor binding and activation of receptor tyrosine kinase and subsequent activation of intracellular insulin receptor substrate-1 (IRS1); however, insulin and IGF1-mediated signaling pathways are also implicated in pathogenesis and progression of several cancers via the activation of the Ras/Raf/MEK/ERK, PI3K/Akt/mTORC1, and GSK3β/β-catenin pathways [5,44].…”

Section: Biology Of Metformin and Molecular Mechanism Of Actionmentioning

confidence: 99%

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Metformin: The Answer to Cancer in a Flower? Current Knowledge and Future Prospects of Metformin as an Anti-Cancer Agent in Breast Cancer

et al. 2019

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Interest has grown in studying the possible use of well-known anti-diabetic drugs as anti-cancer agents individually or in combination with, frequently used, chemotherapeutic agents and/or radiation, owing to the fact that diabetes heightens the risk, incidence, and rapid progression of cancers, including breast cancer, in an individual. In this regard, metformin (1, 1-dimethylbiguanide), well known as ‘Glucophage’ among diabetics, was reported to be cancer preventive while also being a potent anti-proliferative and anti-cancer agent. While meta-analysis studies reported a lower risk and incidence of breast cancer among diabetic individuals on a metformin treatment regimen, several in vitro, pre-clinical, and clinical studies reported the efficacy of using metformin individually as an anti-cancer/anti-tumor agent or in combination with chemotherapeutic drugs or radiation in the treatment of different forms of breast cancer. However, unanswered questions remain with regards to areas such as cancer treatment specific therapeutic dosing of metformin, specificity to cancer cells at high concentrations, resistance to metformin therapy, efficacy of combinatory therapeutic approaches, post-therapeutic relapse of the disease, and efficacy in cancer prevention in non-diabetic individuals. In the current article, we discuss the biology of metformin and its molecular mechanism of action, the existing cellular, pre-clinical, and clinical studies that have tested the anti-tumor potential of metformin as a potential anti-cancer/anti-tumor agent in breast cancer therapy, and outline the future prospects and directions for a better understanding and re-purposing of metformin as an anti-cancer drug in the treatment of breast cancer.

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Section: Efficacy In Non-diabetic Patients and Non-diabetic Cancer Pamentioning

confidence: 98%

Section: Biology Of Metformin and Molecular Mechanism Of Actionmentioning

confidence: 99%

Metformin: The Answer to Cancer in a Flower? Current Knowledge and Future Prospects of Metformin as an Anti-Cancer Agent in Breast Cancer

et al. 2019

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“…Metformin gewinnt derzeit aufgrund interessanter pleiotroper Effekte, die Änderungen des Epigenoms und der Genexpression beeinflussen und so potenziell protektiv u. a. gegen Karzinome wirken sollen, großes Interesse [45][46][47][48][49][50][51].…”

Section: Menschen Mit Typ-2-diabetesunclassified

Therapie des Typ-2-Diabetes

Landgraf

Aberle

Birkenfeld

et al. 2020

Diabetologie und Stoffwechsel

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“…Metformin is currently gaining great interest due to interesting pleiotropic effects that influence changes at the epigenetic level and gene expression and are thus potentially protective against carcinomas [39][40][41][42][43][44].…”

Section: Metforminmentioning

confidence: 99%

Therapy of Type 2 Diabetes

Landgraf

Aberle

Birkenfeld

et al. 2019

Exp Clin Endocrinol Diabetes

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The practical recommendations of the German Diabetes Society/ Deutsche Diabetes Gesellschaft (DDG) together with the German Society for Internal Medicine/Deutschen Gesellschaft für Innere Medizin (DGIM) are based on the contents of the National Treatment Guideline (Nationale Versorgungsleitlinie NVL) "Therapy of Type 2 Diabetes" [1]. The modifications in therapy and their justifications made in the present DDG practical recommendations were updated on the basis of new randomized controlled trials (RCTs) and meta-analyses and were consented by the DDG and the DGIM. Definition of Type 2 DiabetesType 2 diabetes is a chronic, very heterogeneous, multi-factorial, progressive disease characterized by inherited and acquired insulin resistance and qualitative and quantitative insulin secretion disturbances.Influenceable and uninfluenceable risk factors for type 2 diabetes are listed in the "Risk factors for type 2 diabetes" infobox. Therapeutic goalsIn the present recommendations, target ranges are identified which -with varying levels of strengths of evidence -inform the physician and the patient on which target range/target value should be aimed for according to current medical knowledge based on evidence and consensus. The main objective remains to set individual therapy goals primarily together with the patient and possibly his or her relatives and agreeing them optimally in writing on a quarterly basis (e. g. in the Health Passport Diabetes). General and specific therapeutic goalsThe therapeutic goals of people with type 2 diabetes depend on patient preference, comorbidity, duration of the disease, age and life expectancy, quality of life, cultural conditions, psychosocial circumstances and possibilities as well as abilities of the persons S73This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.

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The effect of metformin on biomarkers associated with breast cancer outcomes: a systematic review, meta-analysis, and dose–response of randomized clinical trials

Abstract: This document is the author's post-print version, incorporating any revisions agreed during the peer-review process. Some differences between the published version and this version may remain and you are advised to consult the published version if you wish to cite from it.

Cited by 33 publications

References 54 publications

Metformin: The Answer to Cancer in a Flower? Current Knowledge and Future Prospects of Metformin as an Anti-Cancer Agent in Breast Cancer

Metformin: The Answer to Cancer in a Flower? Current Knowledge and Future Prospects of Metformin as an Anti-Cancer Agent in Breast Cancer

Therapie des Typ-2-Diabetes

Therapy of Type 2 Diabetes

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