Journal Article

Insulin/IGF Axis in Breast Cancer: Clinical Evidence and Translational Insights

Biello, Federica, D’Avanzo, Francesca, Martini, Veronica, Gennari, Alessandra, Marzullo, Paolo, Cattrini, Carlo, Mennitto, Alessia, Genestroni, Silvia, Aimaretti, Gianluca, Platini, Francesca

2021

Overview

Background: Breast cancer (BC) is the most common neoplasm in women. Many clinical and preclinical studies investigated the possible relationship between host metabolism and BC. Significant differences among BC subtypes have been reported for glucose metabolism. Insulin can promote tumorigenesis through a direct effect on epithelial tissues or indirectly by affecting the levels of other modulators, such as the insulin-like growth factor (IGF) family of receptors, sex hormones, and adipokines. The potential anti-cancer activity of metformin is based on two principal effects: first, its capacity for lowering circulating insulin levels with indirect endocrine effects that may impact on tumor cell proliferation; second, its direct influence on many pro-cancer signaling pathways that are key drivers of BC aggressiveness. Methods: In the present review, the interaction between BC, host metabolism, and patients’ prognosis has been reviewed across available literature evidence. Conclusions: Obesity, metabolic syndrome, and insulin resistance are all involved in BC growth and could have a relevant impact on prognosis. All these factors act through a pro-inflammatory state, mediated by cytokines originated in fat tissue, and seem to be related to a higher risk of BC development and worse prognosis.

• Publisher: MDPI AG,MDPI
• Subject: BMI / Breast cancer / Cell growth / Cell proliferation / Cytokines / Glucose metabolism / Hormones / host metabolism / IGF / Inflammation / Insulin / Insulin resistance / Insulin-like growth factors / Metabolic syndrome / Metformin / Neoplasia / Obesity / Prognosis / Review / Sex hormones / Tumorigenesis