Korean Journal of Clinical Pharmacy (한국임상약학회지)

Korean College Of Clinical Pharmacy (한국임상약학회)
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Effects of Metformin on Breast Cancer Risk and Mortality in Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis

제 2형 당뇨병 환자의 유방암 발생 위험 및 사망률에 대한 메트포민의 영향: 체계적 문헌고찰 및 메타분석

  • Received : 2015.03.31
  • Accepted : 2015.08.12
  • Published : 2015.09.30
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Abstract

Background: The protective effect of metformin against breast cancer is inconclusive. Objective: To evaluate the effect of metformin on breast cancer risk and mortality in patients with type 2 diabetes. Method: A comprehensive literature search was performed for pertinent articles published prior to June 30, 2014, using PubMed and EMBASE. Study heterogeneity was estimated with $I^2$ statistic. The data from the included studies were pooled and weighted by random-effects model. The quality of each included study was assessed on the basis of the 9-star Newcastle-Ottawa Scale and publication bias was evaluated by visual inspection of a funnel plot. Results: Ten studies were included in the meta-analysis of the association of metformin and breast cancer risk. By synthesizing the data from the studies, the pooled odds ratio (OR) was 0.72 (95% CI: 0.59, 0.87) (p = 0.0005). Three cohort studies were included for meta-analysis of the association between metformin and breast cancer-related mortality. Metformin was associated with a significant decrease in mortality (Risk ratio: 0.68; 95% CI: 0.51, 0.90, p = 0.007). Conclusion: The present meta-analysis suggests that metformin appears to be associated with a lower risk of breast cancer incidence and mortality in patients with type 2 diabetes.

Keywords

References

  1. American Diabetes Association. Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2008;31(Suppl 1):S55-60. https://doi.org/10.2337/dc08-S055
  2. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin 2011;61:69. https://doi.org/10.3322/caac.20107
  3. Moolgavkar SH, Day NE, Stevens RG. Two-stage model for carcinogenesis: Epidemiology of breast cancer in females. J Natl Cancer Inst 1980;65:559-69.
  4. Colditz GA, Rosner B. Cumulative risk of breast cancer to age 70 years according to risk factor status: data from the Nurses' Health Study. Am J Epidemiol 2000;152:950-64. https://doi.org/10.1093/aje/152.10.950
  5. Eliassen AH, Colditz GA, Rosner B, et al. Adult weight change and risk of postmenopausal breast cancer. JAMA 2006;296:193-201. https://doi.org/10.1001/jama.296.2.193
  6. Boyd NF, Guo H, Martin LJ, et al. Mammographic density and the risk and detection of breast cancer. N Engl J Med 2007;356:227-36. https://doi.org/10.1056/NEJMoa062790
  7. Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 2007;25:1329-33. https://doi.org/10.1200/JCO.2006.09.1066
  8. Resta F, Triggiani V, Sabba C, et al. The impact of body mass index and type 2 diabetes on breast cancer: current therapeutic measures of prevention. Curr Drug Targets Immune Endocr Metabol Disord 2004;4: 327-33. https://doi.org/10.2174/1568008043339686
  9. Key TJ, Verkasalo PK, Banks E. Epidemiology of breast cancer. Lancet Oncol 2001;2:133-40. https://doi.org/10.1016/S1470-2045(00)00254-0
  10. Baron JA, Weiderpass E, Newcomb PA, et al. Metabolic disorders and breast cancer risk (United States). Cancer Causes Control 2001;12:875-80. https://doi.org/10.1023/A:1013796112348
  11. Lipscombe LL, Goodwin PJ, Zinman B, et al. Increased prevalence of prior breast cancer in women with newly diagnosed diabetes. Breast Cancer Res Treat 2006;98:303-9. https://doi.org/10.1007/s10549-006-9166-3
  12. Arcidiacono B, Iiritano S, Nocera A, et al. Insulin resistance and cancer risk: an overview of the pathogenetic mechanisms. Exp Diabetes Res 2012;2012:789174.
  13. Zakikhani M, Dowling R, Fantus IG, et al. Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. Cancer Res 2006;66:10269-73. https://doi.org/10.1158/0008-5472.CAN-06-1500
  14. Hundal RS, Krssak M, Dufour S, et al. Mechanism by which metformin reduces glucose production in type 2 diabetes. Diabetes 2000;49:2063-9. https://doi.org/10.2337/diabetes.49.12.2063
  15. Lee JH, Kim TI, Jeon SM, et al. The effects of metformin on the survival of colorectal cancer patients with diabetes mellitus. Int J Cancer 2012;131:752-9. https://doi.org/10.1002/ijc.26421
  16. Kourelis TV, Siegel RD. Metformin and cancer: new applications for an old drug. Med Oncol 2012;29:1314-27. https://doi.org/10.1007/s12032-011-9846-7
  17. Bodmer M, Becker C, Meier C, et al. Use of metformin is not associated with a decreased risk of colorectal cancer: a case-control analysis. Cancer Epidemiol Biomarkers Prev 2012;21:280-6. https://doi.org/10.1158/1055-9965.EPI-11-0992-T
  18. Ladson G, Dodson WC, Sweet SD, et al. The effects of metformin with lifestyle therapy in polycystic ovary syndrome: a randomized doubleblind study. Fertil Steril 2011;95:1059-66. https://doi.org/10.1016/j.fertnstert.2010.12.002
  19. Wells GA, Shea B, O'Connell D, et al. The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analysis. Ottawa Health Research Institute. http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm (Accessed on Aug 25, 2014).
  20. Zheng JS, Hu XJ, Zhao YM, et al. Intake of fish and marine n-3 polyunsaturated fatty acids and risk of breast cancer: meta-analysis of data from 21 independent prospective cohort studies. BMJ 2013;346:f3706. https://doi.org/10.1136/bmj.f3706
  21. Libby G, Donnelly LA, Donnan PT, et al. New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes Care 2009;32:1620-5. https://doi.org/10.2337/dc08-2175
  22. Bodmer M, Meier C, Krahenbuhl S, Jick SS, et al. Long-term metformin use is associated with decreased risk of breast cancer. Diabetes Care 2010;33:1304-8. https://doi.org/10.2337/dc09-1791
  23. Bosco JL, Antonsen S, Sorensen HT, et al. Metformin and incident breast cancer among diabetic women: a population-based case-control study in Denmark. Cancer Epidemiol Biomarkers Prev 2011;20:101-11. https://doi.org/10.1158/1055-9965.EPI-10-0817
  24. Ruiter R, Visser LE, van Herk-Sukel MP, et al. Lower risk of cancer in patients on metformin in comparison with those on sulfonylurea derivatives: results from a large population-based follow-up study. Diabetes Care 2012;35:119-24. https://doi.org/10.2337/dc11-0857
  25. Bayraktar S, Hernadez-Aya LF, Lei X, et al. Effect of metformin on survival outcomes in diabetic patients with triple receptor-negative breast cancer. Cancer 2012;118:1202-11. https://doi.org/10.1002/cncr.26439
  26. Hsieh MC, Lee TC, Cheng SM, et al. The influence of type 2 diabetes and glucose-lowering therapies on cancer risk in the Taiwanese. Exp Diabetes Res 2012;2012:413782.
  27. Qiu H, Rhoads GG, Berlin JA, et al. Initial metformin or sulphonylurea exposure and cancer occurrence among patients with type 2 diabetes mellitus. Diabetes Obes Metab 2013;15:349-57. https://doi.org/10.1111/dom.12036
  28. Redaniel MT, Jeffreys M, May MT, et al. Associations of type 2 diabetes and diabetes treatment with breast cancer risk and mortality: a population-based cohort study among British women. Cancer Causes Control 2012;23:1785-95. https://doi.org/10.1007/s10552-012-0057-0
  29. Tsilidis KK, Capothanassi D, Allen NE, et al. Metformin Does Not Affect Cancer Risk: A Cohort Study in the U.K. Clinical Practice Research Datalink Analyzed Like an Intention-to-Treat Trial. Diabetes Care 2014;37:2522-32. https://doi.org/10.2337/dc14-0584
  30. Tseng CH. Metformin may reduce breast cancer risk in Taiwanese women with type 2 diabetes. Breast Cancer Res Treat 2014;145:785-90. https://doi.org/10.1007/s10549-014-2985-8
  31. Lega IC, Austin PC, Gruneir A, et al. Association between metformin therapy and mortality after breast cancer: a population-based study. Diabetes Care 2013;36:3018-26. https://doi.org/10.2337/dc12-2535
  32. Hou G, Zhang S, Zhang X, et al. Use of metformin and survival of diabetic women with breast cancer. Curr Drug Saf 2013;8:357-63. https://doi.org/10.2174/15680266113136660069
  33. Green AS, Chapuis N, Lacombe C, et al. LKB1/AMPK/mTOR signaling pathway in hematological malignancies: from metabolism to cancer cell biology. Cell Cycle 2011;10(13):2115-20. https://doi.org/10.4161/cc.10.13.16244
  34. Goodwin PJ, Stambolic V. Obesity and insulin resistance in breast cancer--chemoprevention strategies with a focus on metformin. Breast 2011;20(Suppl 3):S31-5.
  35. Col NF, Ochs L, Springmann V, et al. Metformin and breast cancer risk: a meta-analysis and critical literature review. Breast Cancer Res Treat 2012;135(3):639-46. https://doi.org/10.1007/s10549-012-2170-x
  36. Currie CJ, Poole CD, Gale EA. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia 2009;52(9):1766-77. https://doi.org/10.1007/s00125-009-1440-6
  37. Col NF, Ochs L, Springmann V, et al. Glucose lowering agents and the patterns of risk for cancer: a study with the General Practice Research Database and secondary care data. Diabetologia 2012;55(3):654-65. https://doi.org/10.1007/s00125-011-2390-3
  38. Staa Van, Patel D, Gallagher AM, de Bruin ML. Diabetes, metformin, and breast cancer in postmenopausal women. J Clin Oncol 2012; 30:2844-52. https://doi.org/10.1200/JCO.2011.39.7505
  39. DeCensi A, Puntoni M, Goodwin P, et al. Metformin and cancer risk in diabetic patients: a systematic review and meta-analysis. Cancer Prev Res (Phila) 2010;3(11):1451-61. https://doi.org/10.1158/1940-6207.CAPR-10-0157
  40. Stevens RJ, Ali R, Bankhead CR, et al. Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials. Diabetologia 2012;55(10):2593-603. https://doi.org/10.1007/s00125-012-2653-7
  41. Noto H, Goto A, Tsujimoto T, Noda M. Cancer risk in diabetic patients treated with metformin: a systematic review and meta-analysis. PLoS One 2012;7(3):e33411. https://doi.org/10.1371/journal.pone.0033411
  42. Bowker SL, Majumdar SR, Veugelers P, et al. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care 2006;29(2):254-8. https://doi.org/10.2337/diacare.29.02.06.dc05-1558
  43. Landman GW, Kleefstra N, van Hateren KJ, et al. Metformin associated with lower cancer mortality in type 2 diabetes: ZODIAC-16. Diabetes Care 2010;33(2):322-6. https://doi.org/10.2337/dc09-1380
  44. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998;352(9131):854-65. https://doi.org/10.1016/S0140-6736(98)07037-8
  45. Mellbin LG, Malmberg K, Norhammar A, et al. Prognostic implications of glucose-lowering treatment in patients with acute myocardial infarction and diabetes: experiences from an extended follow-up of the Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 Study. Diabetologia 2011;54(6):1308-17. https://doi.org/10.1007/s00125-011-2084-x