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Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention

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Research Article

Association of metformin with breast cancer incidence and mortality in patients with type 2 diabetes: a GRADE assessed systematic review and meta-analysis

Grace H Tang, Meloja Satkunam, Gregory R Pond, Gregory R Steinberg, Giovanni Blandino, Holger J. Schünemann and Paola Muti
Grace H Tang
Health Sciences, McMaster University
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Meloja Satkunam
Health Sciences, McMaster University
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Gregory R Pond
Department of Oncology, Faculty of Health Science, McMaster University
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Gregory R Steinberg
Department of Medicine, McMaster University
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Giovanni Blandino
National Cancer Institute Regina Elena
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Holger J. Schünemann
Health Sciences, McMaster University
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Paola Muti
Department of Oncology, Faculty of Health Science, McMaster University
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  • For correspondence: muti@mcmaster.ca
DOI: 10.1158/1055-9965.EPI-17-0936
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Abstract

Background: Preclinical data suggests that metformin may reduce breast cancer incidence and improve cancer prognosis. However, the current evidence in observational studies is inconclusive. A systematic review and meta-analysis was conducted to assess the effect of metformin on the incidence of breast cancer and all-cause mortality in patients with type 2 diabetes (T2D). Methods: A literature search was performed on Medline, EMBASE, and the Cochrane library from inception to November 2016. Outcomes were incidence of breast cancer and all-cause mortality. Risk of bias and overall certainty of evidence was assessed using the Newcastle Ottawa Scale and GRADE, respectively. Meta-analyses were performed using the most fully adjusted odds ratios (ORs) or hazard ratios (HRs) and 95% confidence intervals (95% CI) as effect measures. Results: A total of 12 observational studies were included for breast cancer incidence and 11 studies for all-cause mortality. No significant association was found between metformin exposure and incidence of breast cancer (OR: 0.93, 95%CI: 0.85-1.03, I2 = 35%). A 45% risk reduction was observed for all-cause mortality (HR: 0.55, 95%CI: 0.44-0.70, I2=81%). Presence of publication bias is strongly suspected for both outcomes using Egger's funnel plots. Conclusions: The use of metformin may improve overall survival in patients with T2D and breast cancer. No effect of metformin on the incidence of breast cancer was observed. Interpretation of results is limited by the observational nature of the studies and resulting biases. Impact: Clinical trials are warranted to determine the role of metformin in breast cancer risk reduction and prognosis.

  • Received October 11, 2017.
  • Revision received December 15, 2017.
  • Accepted March 30, 2018.
  • Copyright ©2018, American Association for Cancer Research.

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Published OnlineFirst April 4, 2018
doi: 10.1158/1055-9965.EPI-17-0936

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Association of metformin with breast cancer incidence and mortality in patients with type 2 diabetes: a GRADE assessed systematic review and meta-analysis
Grace H Tang, Meloja Satkunam, Gregory R Pond, Gregory R Steinberg, Giovanni Blandino, Holger J. Schünemann and Paola Muti
Cancer Epidemiol Biomarkers Prev April 4 2018 DOI: 10.1158/1055-9965.EPI-17-0936

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Association of metformin with breast cancer incidence and mortality in patients with type 2 diabetes: a GRADE assessed systematic review and meta-analysis
Grace H Tang, Meloja Satkunam, Gregory R Pond, Gregory R Steinberg, Giovanni Blandino, Holger J. Schünemann and Paola Muti
Cancer Epidemiol Biomarkers Prev April 4 2018 DOI: 10.1158/1055-9965.EPI-17-0936
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Cancer Epidemiology, Biomarkers & Prevention
eISSN: 1538-7755
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