Metformin For Prolonging Overall Survival In Patients With Breast Cancer Complicated With Diabetes:A Meta-Analysis

Background:Recent epidemiological studies have shown that diabetes mellitus can increase the risk of breast cancer in patients.As the first-line recommended drug for treatment of type 2 diabetes mellitus,metformin can reduce not only blood sugar,but also the incidence of solid tumors such as prostate cancer,colorectal cancer and gynecological cancer.Mortality rates have different effects,of which breast cancer has a unique role.For those patients with diabetes without breast cancer who received metformin,those who received metformin and neoadjuvant therapy had a higher rate of complete pathologic remission.However,this result has not been reconfirmed in the same type of study.We therefore performed an updated meta-analysis to assess the effect of the addition of metformin on the prognosis of patients with breast cancer with diabetes.Methods:We searched Pubmed,Embase,Cochrane databases.Collected all the English articles published since the establishment of the database until December 2017 on the prognosis of patients with breast cancer with diabetes mellitus and even with metformin in patients with simple breast cancer without diabetes mellitus,including case-control studies,retrospective case studies and randomized controls trail,etc.,no crowd,race,length of follow-up,sample size and other restrictions.We conducted a meta-analysis using random effects models,hazard ratio(HR),and 95%confidence interval(95%confidence interval)as effect measures.In addition,we conducted a subgroup analysis and sensitivity analysis in order to estimate whether the overall combined effect was reliable and robust enough.Results:A total of 8 articles,including 11 different populations,were included in our meta-analysis.A total of 49,462 participants,including 2,172 breast cancer patients with type 2 diabetes who received metformin,did not receive metformin for breast cancer.There were 2078 patients with type 2 diabetes,and there were 45,212 breast cancer patients without diabetes.The meta-analysis showed that the metformin group had a longer overall survival compared with the non-received group(HR:0.54;95%CI:0.38-0.78;I~2=80.4%);similarly,the group receiving metformin still had better survival benefit(HR:0.71;95%CI:0.58-0.87;I~2=40.8%).Subsequent subgroup analysis and sensitivity analysis conducted by us all proved the reliability and stability of the results.Conclusion:Current research shows that metformin treatment may prolong the overall survival of breast cancer patients with type 2 diabetes.However,this result needs to be carefully interpreted.Our research results also need more high-quality prospective studies or randomized controlled trials to further verify.