Insulin Receptor Expression and its Association with Hyperinsulinemia in Triple Negative Breast Cancer

Abstract Purpose Hyperinsulinemia and tumor insulin receptor (IR) expression have been associated with triple negative breast cancer (TNBC) progression in pre-clinical models. We aimed to evaluate the expression of the IR, insulin-like growth factor 1 receptor (IGF-1R), and associated signaling protein expression in TNBC, and their correlations with demographic and metabolic parameters in a population of women with TNBC. Methods We identified cases of TNBC from our multi-institutional, cross-sectional study of self-identified Black and White women with newly diagnosed breast cancer. Survey, anthropometric, screening behavior, laboratory, and tumor pathology reports were collected, along with formalin fixed paraffin embedded tumor samples. We performed immunohistochemistry (IHC) analysis and quantified the expression of IR, IGF-1R, phosphorylated Erk1/2 (pErk1/2) and FOXO3a. Clinical information was correlated with IHC scoring. Results There were 93 TNBC cases. IHC staining and quantification found that 63% of TNBC cases stained positive for IR, 73% for IGF-1R, 67% for FOXO3a and 43% for pErk1/2. Positive IR staining was more prevalent in Black women than White women (p=0.003), and was associated with body mass index, and fasting insulin on univariate analysis, but was not significantly associated with age. On multivariate analysis IR expression was associated with fasting insulin, but not race. IGF-1R, FOXO3a, and pErk1/2 staining were not associated with any of these factors. Conclusions Tumor IR expression was associated with higher fasting insulin, and higher fasting insulin was more prevalent among Black women. Further studies are needed to determine the importance of hyperinsulinemia, tumor IR expression in the development of TNBC.