INSR and obesity due to melanocortin 4 receptor deficiency: Hyperinsulinemia has become a research hotspot as a potential mediator for the growth of obesity-related BC, and the increased plasma levels of insulin independently predict the increased risk and mortality in obesity-related tumors, including BC and several other tumor types (17, 55) Obesity-related hyperinsulinemia could lead to the abnormal insulin signaling pathway, which may affect the expression and localization of insulin receptor (InsR), in BC (56).