8212 Insulin Receptor Signaling and Racial Disparities in Triple Negative Breast Cancer

• Published in: Journal of the Endocrine Society 2024-10, Vol.8 (Supplement_1)
• Main Authors: Engel, A J, Samuel, K, Bass, I R, Lin, S, Antoniou, I, Yagnik, R, LeRoith, D, Bickell, N A, Gallagher, E J
• Format: Article
• Language: English
• Subjects: Abstract
• ISSN: 2472-1972; 2472-1972
• DOI: 10.1210/jendso/bvae163.2259

Abstract Disclosure: A.J. Engel: None. K. Samuel: None. I.R. Bass: None. S. Lin: None. I. Antoniou: None. R. Yagnik: None. D. LeRoith: None. N.A. Bickell: None. E.J. Gallagher: Consulting Fee; Self; Novartis Pharmaceuticals. Introduction: Obesity and type 2 diabetes are associated with poor breast cancer (BC) prognosis. These disorders, along with hyperinsulinemia are more common in Black than in White women. Black women also have higher rates of triple negative breast cancer (TNBC), and greater breast cancer mortality than White women. We hypothesized that Black women with TNBC have worse outcomes in part due to tumor promoting effects of hyperinsulinemia via the insulin receptor (IR) signaling pathway. Methods: From our IRB-approved, multi-institutional, cross-sectional, NIH-funded, study of women with newly diagnosed BC, we identified women with TNBC. We performed immunohistochemistry (IHC) analysis of formalin-fixed-paraffin-embedded tumor samples from 45 self-identified Black women and 48 self-identified White women. We quantified the BC expression of IR (n=92), IGF1R (n=92), pERK (n=91), FOXO3a (n=90) for intensity (none=0, weak=1, moderate=2, intense=3). In subsequent analysis, 0 and 1 intensity IHC staining were considered negative, and 2 and 3 were considered positive. Quantification was performed with reviewers blinded to clinical information. Clinical information (age, race, body mass index [BMI], waist circumference, fasting insulin, BC Nottingham Prognostic Index [NPI]) was evaluated after IHC scoring. Statistical proportions were compared using Fishers Exact test, and continuous variables were evaluated using parametric or non-parametric tests, as appropriate. Results: Positive IR staining was seen in 64% of samples (n=59), 74% (n=68) for IGF1R, 68% (n=62) for FOXO3a and 43.3% (n=39) for pERK. Positive IR staining was more prevalent in Black women than White women (P=0.003) but was not significantly associated with age or NPI. IGF1R, FOXO3a, pERK positive staining were not associated with race or NPI. Positive IR staining was also associated with higher BMI, waist circumference, and fasting insulin (P