Metformin for the treatment of breast cancer: a scoping review of randomized clinical trials

Metformin has been the focus of substantial interest in the field of oncology. Although breast cancer is the type of cancer where metformin was most extensively-studied through randomized clinical trials (RCTs), none of the previous reviews in this field provided a comprehensive overview of the landscape of RCTs taking into account the phenotype of breast cancer, its staging, and treatment modalities. This scoping review sought to comprehensively map the literature of RCTs focusing on the use of metformin in the treatment of breast cancer and followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Extension for Scoping Reviews guidelines. The eligibility criteria encompassed all RCTs involving metformin for adult patients with breast cancer, with no constraints regarding context, language, publication date, or outcomes. We included 122 reports from 40 RCTs comprising a total of 5,623 participants and 107 distinct outcomes. The results showed that most studies did not present results by phenotype of breast cancer and highlighted critical gaps and opportunities in the literature. Notably, limited evidence from subgroup analyses within a large RCT suggested potential benefits of metformin in improving overall and disease-free survival among HER2+ participants but not among patients with other phenotypes. Our findings highlight the potential for considerably expanding the current knowledge base in this field through the retrospective determination of participant phenotypes, facilitating cost-effective and time-efficient individual participant data meta-analyses. Furthermore, we recommend that funding agencies and journals mandate the comprehensive presentation of results from RCTs on breast cancer based on phenotype.