Abstract 3264: IGF-axis protein expression and survival in Native Hawaiian breast cancer patients

Abstract

Abstract Obesity-induced and related aberrations in insulin signaling may contribute to differences in breast cancer risk and outcome across racial/ethnic populations. The mechanisms underlying breast cancer disparities among Asian and Pacific Islander populations in the U.S. (specifically the high risk and poor survival of Native Hawaiians) are unknown. We examined the expression of IGF-axis proteins (IGF1, IGF1R, IGFBP2, and IGFBP3) in archived tumor tissue from 358 invasive breast cancer patients diagnosed in Hawaii. Overall and breast cancer-specific survival were evaluated via Kaplan-Meier curves and Cox's proportional hazards regression. Covariates included demographic and clinical factors, ER/PR/HER2 status, and for a subset of patients participating in the Multiethnic Cohort (MEC) (n=104), history of obesity, diabetes, and estrogen use at baseline. Across all cases, expression of the IGF-axis proteins in tumors did not differ by race/ethnicity. In the MEC subset, IGF1 expression was observed in 22% of estrogen users compared to 46% of non-users (p=0.04) and expression of IGFBP2 was observed in 71% of estrogen users compared to 93% of non-users (p=0.02). Protein expression did not vary by body mass index (BMI) or diabetes history. Obesity was most prevalent in Native Hawaiians (72%) and lowest in Japanese Americans (2%) (p<0.0001). History of estrogen use was highest in whites (73%) and lowest in Native Hawaiians (28%) (p=0.008). Across all MEC patients, IGFBP2 expression was associated with shorter breast cancer-specific survival after adjustment for age, stage, first-course of treatment, ER, PR, HER2, and estrogen use (HR=2.23, 95% CI 1.03-4.85). When examined by individual race/ethnic groups across all patients, overall and breast cancer-specific survival did not vary by IGF-axis protein expression for whites, Japanese, Filipinos, or Chinese. Among Native Hawaiians, IGFBP2 and IGFBP3 expression was associated with shorter overall survival when adjusted for age, stage, first-course of treatment, ER, PR, and HER2 (HR=10.04, 95% CI 2.13-47.50 and HR=3.40, 95% CI 1.05-10.99, respectively). In the MEC subset, the associations remained after additional adjustment for BMI (HR=16.30, 95% CI 2.84-93.40 and HR=4.64, 95% CI 1.30-16.59, respectively). IGFBP3 was also associated with a poorer breast cancer-specific survival in Native Hawaiian women when adjusted for age, stage, first-course of treatment, ER, PR, and HER2 (HR=2.79, 95% CI 1.12-6.93), and additional adjustment for BMI (HR=3.03, 95% CI 1.19-7.34). IGF1R expression was significantly inversely associated with overall survival among Native Hawaiians after adjustment for age, stage, first-course of treatment, ER, PR, HER2, and BMI (HR=14.46, 95% CI 2.26-92.57). In the analyses of individual race/ethnic groups, null cell sizes precluded the evaluation of estrogen use as a covariate. Aberrant insulin-signaling may influence outcomes in Native Hawaiian breast cancer patients. Citation Format: Brenda Y. Hernandez, Lynne R. Wilkens, Loic Le Marchand, David Horio, Clayton D. Chong, Lenora W. M. Loo. IGF-axis protein expression and survival in Native Hawaiian breast cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3264. doi:10.1158/1538-7445.AM2014-3264