Abstract
Background: Plasma concentrations of insulin-like growth factors (IGFs) and adipokines have been extensively studied with regards to their associations with breast cancer risk. Conversely, little is known about how the levels of these hormones in the breast influence tissue microenvironment and breast cancer risk. In this study, we measured IGFs and adipokines in breast tissues and investigated the relationship between tissue and plasma hormone concentrations and the homogeneity of these hormones within the breast. Methods: Sixty tissue samples were available for study (from fifteen reduction mammoplasty subjects). Four samples from each participant were studied: three samples from one breast (upper section, UP; lower section, LO; and center, CT) and one sample from the opposite breast. Total protein was extracted from frozen tissues. Protein concentration was determined by coomassie assay. Tissue and plasma IGF-1 and IGFBP-3 were quantified using the Immulite 1000; leptin and adiponectin concentrations were quantified using commercially available ELISAs. Tissue hormone levels measured by the immunoassays were divided by total protein concentration and are reported in nanograms of hormone per milligram of protein (ng/mg of protein) and plasma concentrations are reported as nanograms per milliliter (ng/ml). Assays were highly reproducible and all CVs were below 7.5%. Spearman correlation coefficients were used to describe the associations between mean tissue hormone levels and plasma concentrations. We used Spearman correlations and the Friedman test to test for differences among hormone levels in various breast sections. Results: In this group, tissue IGF-1 levels ranged from 3.75-29.20 ng/mg of protein; IGFBP-3 5.17-22.14 ng/mg of protein; leptin 0.03-1.51 ng/mg of protein; and adiponectin 39.76-439.42 ng/mg of protein. We observed that there was no major difference in hormone levels among breast sections for leptin, adiponectin, IGF-1, and IGFBP-3 (Friedman p-value= 0.29, 0.54, 0.09, and 0.62, respectively). We observed inverse relationships between mean tissue level and plasma IGF-1 and IGFBP-3 (r=-0.30, p-value=0.26 and r=-0.03, p-value=0.90, respectively), but these relationships were not statistically significant. On the other hand, we observed a positive association between mean tissue level and plasma leptin and adiponectin (r=0.70, p-value=0.004 and r=0.44, p-value=0.10), but only the leptin association was found to be statistically significant. Conclusions: We have shown that hormone levels are homogeneous within the breast. Our data indicates a lack of correlation between mean tissue and plasma IGF-1, IGFBP-3, and adiponectin and suggests a high correlation between mean tissue and plasma leptin. We are currently investigating these associations in a larger population to determine if these observations remain consistent.
Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4873.
100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO