Factors influencing the anticancer effects of metformin on breast cancer outcomes: a systematic review and meta-analysis. Issue 4 (3rd April 2022) - Barakat, Hadeer Ehab
ABSTRACT: Introduction: Several clinical trials have attempted to find evidence that supports the use of metformin as an anticancer treatment. However, the observed effects on various breast cancer (BC) outcomes have been heterogeneous. Areas covered: Based on the outcomes of previous clinical trials, this review discusses the patients' characteristics, cancer intrinsic subtypes, cancer stage, and anticancer treatments that may influence the anticancer effect of metformin on BC outcomes. Additionally, the safety and tolerability of metformin addition to various anticancer regimens are reviewed. Expert opinion: Metformin is a challenging anticancer agent in BC cohorts, besides being safe and well-tolerated at antidiabetic doses. Survival benefits of metformin have been observed in BC patients with: hormone receptor-positive, human epidermal growth factor receptor-2 overexpression, and high insulin like growth factor-1 receptor expression on the tumor surface. Moreover, patients with diabetes receiving metformin experienced better survival outcomes compared to diabetic patients not receiving metformin. Additionally, metformin has anti-proliferative activity in patients with BC who have high insulin resistance and high body mass index. Besides, metformin has been shown to decrease metastatic events, and enhance the level of metabolic- and insulin-related biomarkers associated with carcinogenesis. Finally, most adverse events following metformin treatment were low-grade GIT toxicities.