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Year : 2010  |  Volume : 47  |  Issue : 4  |  Page : 471--472

Metformin: "Old warrior for a new battle"

A Jain 
 Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bangalore - 29, India

Correspondence Address:
A Jain
Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bangalore - 29
India




How to cite this article:
Jain A. Metformin: "Old warrior for a new battle".Indian J Cancer 2010;47:471-472


How to cite this URL:
Jain A. Metformin: "Old warrior for a new battle". Indian J Cancer [serial online] 2010 [cited 2020 Jul 15 ];47:471-472
Available from: http://www.indianjcancer.com/text.asp?2010/47/4/471/73553


Full Text

Sir,

There is a paradigm shift in the oncology treatment protocols in recent times. As the translational oncology is evolving, newer targeted therapies are emerging from laboratory to bedside. The darker side of this development is the increasing cost of oncology care both in developed and developing world. Therefore, there is an urgent need for cost-effective management strategies in the field of oncology.

Metformin is a conventional drug used in the management of type 2 diabetes mellitus. Recently, it has shown promising results in breast cancer patients, thus broadening its indications.

Jiralerspong et al, have recently published a retrospective analysis of metformin-treated diabetic patients who received neoadjuvant chemotherapy for early stage breast cancer. The pathologic complete response (pCR) was (24%; 95% CI: 13-34%) in the metformin group, (8%; 95% CI: 2.3-14%) in the nonmetformin group, and (16%; 95% CI, 15-18%) in the nondiabetic group. Pairwise comparisons between the metformin and nonmetformin groups (P = 0.007) and the nonmetformin and nondiabetic groups (P = 0.04) were significant. In this study, metformin was independently predictive of pCR (odds ratio, 2.95; P = 0.04) after adjustment for diabetes, body mass index, age, stage, grade, receptor status, and neoadjuvant taxane use. [1]

Although cross-comparisons are not advisable, the results of this study need attention because the pCR of metformin group is almost equivalent to taxane combination-induced pCR in the National Surgical Adjuvant Breast and Bowel Project (NSABP)-27 study (24% vs 26%). [2]

There is a strong scientific rationale for these results because in various epidemiologic studies, obesity, hyperinsulinemia, and diabetes are associated with the worst outcome in breast cancer patients. [3] In addition to lowering of insulin levels, metformin also activates adenosine monophosphate-activated protein kinase, which inhibits the mammalian target of rapamycin pathway thus blocking protein translation and cell growth. [4]

Hyperinsulinemia is associated with changes in the levels of insulin-like growth factors, sex hormones, and adipokines contributing to tumorigenesis. [3] Metformin partially reverses hyperinsulinemia and may also have antiproliferative mechanism by this action. [5]

There is evidence to suggest that metformin has a positive impact on inflammation and endothelial dysfunction. Metformin was compared with another oral hypoglycemic agent, repaglinide, in nonobese patients with type 2 diabetes and shown to be more effective in reducing the levels of tumor necrosis factor-alpha, plasminogen activator inhibitor-1 antigen, tissue-type plasminogen activator antigen, von Willebrand factor, soluble intercellular adhesion molecule-1, and soluble E-selectin. A further study has shown that metformin is capable of bringing about a significant decrease in the levels of vascular endothelial growth factor and plasminogen activator inhibitor-1. [6],[7],[8]

If confirmed in prospective studies, these results will add a new drug in the management of breast cancer, which is highly cost-effective with fewer side effects.

References

1Jiralerspong S, Palla SL, Giordano SH, Meric-Bernstam F, Liedtke C, Barnett CM, et al. Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J Clin Oncol 2009;27:3297-302.
2Mamounas EP. NSABP Protocol B-27. Preoperative doxorubicin plus cyclophosphamide followed by preoperative or post operative docetaxel. Oncology (Wilson Park) 1997;11:37-40.
3Calle EE, Kaaks R. Overweight, obesity and cancer: Epidemiological evidence and proposed mechanisms. Nat Rev Cancer 2004;4:579-91.
4Goodwin JP, Ligibel JA, Stambolic V. Metformin in Breast Cancer: Time for Action. J Clin Oncol 2009;29:3271-3.
5Goodwin PJ, Pritchard KI, Ennis M, Clemons M, Graham M, Fantus IG. Metformin lowers fasting insulin levels in nondiabetic hyperinsulinemic early stage breast cancer patients. Breast Cancer Res Treat 2006;100:S109.
6Grenader T, Goldberg A, Shavit L. Metformin As an Addition to Conventional Chemotherapy in Breast Cancer. J Clin Oncol 2009;27:e259.
7Lund SS, Tarnow L, Stehouwer CD, Schalkwijk CG, Teerlink T, Gram J, et al. Impact of metformin versus repaglinide on non-glycaemic cardiovascular risk markers related to inflammation and endothelial dysfunction in non-obese patients with type 2 diabetes. Eur J Endocrinol 2008;158:631-41.
8Ersoy C, Kiyici S, Budak F, Oral B, Guclu M, Duran C, et al. The effect of metformin treatment on VEGF and PAI-1 levels in obese type 2 diabetic patients. Diabetes Res Clin Pract 2008;81:56-60.