A Systematic Review and Meta-analysis on the Efficacy and Safety of Metformin as Adjunctive Therapy Among Women with Metastatic Breast Cancer

Breast cancer is the most common cancer among women worldwide and is one of the leading causes of cancer-related mortalities. Metformin has been found to have direct and indirect antitumor mechanisms, and because of its availability and good safety profile, it has been investigated to be useful in various malignancies including breast cancer.This study aims to determine the efficacy and safety of metformin administration as adjunctive therapy on mortality among females with breast cancer.This is a systematic review and meta-analysis of randomized clinical trials (RCTs) on the use of metformin as adjunctive therapy when combined with standard chemotherapy on the outcomes of progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and clinical benefit rate (CBR).After a comprehensive literature search, only three phase 2 RCTs on the use of metformin as adjunctive therapy for locally advanced and metastatic breast cancer were included. Clinical trials on early breast cancer are still ongoing and none were included in the present review. This study, based on the systematic review, revealed that metformin added to standard chemotherapy does not improve the PFS and OS among women with metastatic breast cancer, and likewise, has no impact on the ORR with a relative risk of 1.42 95% CI 0.45-4.55 and CBR with an RR of 0.87, 95% CI 0.55-1.37. It appears to be safe and may even be protective for the development of neutropenia based on at least one study.This study clarifies that there is insufficient evidence on the benefits of metformin on survival among women with metastatic breast cancer.