Metabolic syndrome and triple-negative breast cancer: a new paradigm

Abstract

Triple-negative breast cancers (TNBCs) are aggressive tumors with poor prognosis compared to other breast cancer subtypes. The evidence linking TNBC with the metabolic syndrome, which consists of central obesity, insulin resistance, impaired glucose tolerance, dyslipidemia, and hypertension, has emerged from clinical studies and experiments using cell lines and mouse models. Epidemiological studies have associated abdominal obesity with increased incidence of TNBC. Additionally, insulin resistance, dyslipidemia, and hypertension are associated with increased incidence of breast cancer across all subtypes. The insulin-leptin-adiponectin axis has been implicated mechanistically in breast cancer tumorigenesis. Specifically, increased leptin and decreased adiponectin levels disrupt homeostatic signaling pathways involved in cell proliferation, survival, cell-cycle regulation, and angiogenesis. Insulin, insulin-like growth factor I (IGF-I), and epidermal growth factor receptor (EGFR) may mediate interactions between these two hormones. Further research will facilitate the development of targeted therapeutics and programs to modify lifestyle factors to modulate the insulin-leptin-adiponectin axis for TNBC.

Figure 1

The insulin-leptin-adiponectin axis and risk of TNBC. Schematic representation demonstrates interactions of components in blood. After the compounds enter a normal breast cell, changes in proliferation, survival, cell-cycle regulation, and angiogenesis result in tumorigenesis of either TNBC or non-TNBC. Potential interventions for TNBC, at different levels, are included on the right.