Abstract B93: Racial differences in plasma and breast tissue IGF-1 and IGFBP-3 levels in premenopausal women

Abstract

Abstract Background: Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs), specifically IGF-1 and IGFBP-3 have been extensively studied regarding their role in breast cancer risk. Several studies have shown that higher circulating IGF-1 and IGFBP-3 concentrations in premenopausal women increases breast cancer risk. However, the data have been inconsistent. This may be due to misclassification of tissue levels where blood testing is not an adequate surrogate marker. In this study, we hypothesized that there is a wide interindividual variation in IGF-1 and IGFBP3 breast tissue levels, there will be a low correlation with breast tissue levels and there will be differences between European Americans and African Americans. Methods: Plasma and breast tissues collected from sixty nine premenopausal European American and African American women, without breast cancer, undergoing reduction mammoplasty surgery were analyzed for IGF-1 and IGFBP-3 concentrations. IGF-1 and IGFBP-3 concentrations were quantified using the Immulite 1000 system (Siemens Healthcare Diagnostics, Inc., Los Angeles, CA). Tissue IGF-1 and IGFBP-3 concentrations were adjusted by total protein concentration and are reported as nanograms of hormone per milligram of protein (ng/mg of protein). Assays were highly reproducible and all CVs were ≤9.3%. Spearman rank correlation coefficients were used to describe the associations between plasma and breast tissue IGF-1 and IGFBP-3 concentrations as well as the associations among IGF levels and selected breast cancer risk variables. Wilcoxon Rank-Sum, Kruskal-Wallis, Chi square and Fisher's exact tests were used to describe racial differences. Results: The mean breast tissue levels of IGF-1 in European Americans and African Americans were 21.8±14.2 and 28.5±14.2, respectively. For IGFBP-3 it was 35.0±25.1 and 28.8±26.1. For the IGF-1:IGFBP-3 ratio it was 0.9±0.6 and 1.6±1.0. In European Americans, plasma IGF-1 positively correlated with plasma and tissue IGFBP-3 concentrations (r=0.32; p ≤0.05 and r=0.42; p≤0.05, respectively) and tissue IGF-1 positively correlated with tissue IGFBP-3 concentrations (r= 0.46; p ≤0.05), but in African Americans none of these correlations were significant. Plasma IGFs did not predict tissue level, however several significant associations were observed between the IGFs (particularly the IGF-1:IGFBP-3 ratio) and factors related to body mass, reproductive history and alcohol consumption. Conclusions: Our data show that it is possible to assess endogenous IGFs within the breast tissue microenvironment and that these levels are not well correlated with plasma concentration. There is a wide interindividual variation in tissue levels, only partially predicted by measuring blood levels. Also, African Americans had higher levels than European Americans and so this might be an explanation for some of the differences in breast cancer risk, where African Americans tend to get breast cancer at a younger age. Citation Information: Cancer Prev Res 2010;3(12 Suppl):B93.