The anti-proliferative role of metformin in non-diabetic female patients with breast cancer: Systematic review and meta-analysis of randomized control trials

Abstract

Background. Usage of metformin in non-diabetic women with breast cancer is neither a common approach nor a conventional treatment modality. Metformin and chemotherapy have a high phenotypic variation in complete response rate among diabetic patients with different types of cancer. Although the results on salvage therapy were contradictory, we carried out a meta-analysis to evaluate the effect of the addition of metformin to conventional treatment on the prognosis in non-diabetic women who have breast cancer. Methods. A consummate literature search of Pub-Med, EMBASE, grey literature, and web of science was conducted until 7th of March 2020. A total of 11 randomized control trials were included in this metaanalysis including references related to metformin, breast cancer, and prognosis. The search was limited to English language and human studies, including references related to metformin, breast cancer, and prognosis. We performed the meta-analysis using a random and fixed-effects model, with hazard ratios and 95% confidence intervals (95% CI) as effect measures. Results. A total of 11 randomized control trials consisting of 1681 breast cancer patients without diabetes including 841 ones which received metformintreatement versus 840 ones not treated with metformin. The meta-analysis found that metformin has been linked with anti-proliferative role (HR 0.63, 95% CI 0.59-0.71). Subgroup analysis showed an increased average progression of free survival which demonstrates that metformin improves overall survival by 65% after correcting for hormone-receptor/gene expression (HR 0.35, 95% CI 0.15-0.84). Taking metformin as treatment of breast cancer has been related to extended survival rate. Conclusion. This meta-analysis supports the potential role of metformin in the management of cancer, as it may increase progression free survival among non-diabetic patients with breast cancer. More clinical trials are needed for further exploration of metformin role, and to determine whether improvements in cancer care can be achieved with adding metformin to reduce mortality or to improve overall survival in patients with breast cancer.