Abstract
Abstract Background: One approach to develop new tools for detecting cancer early is through the identification and validation of blood-based cancer specific biomarkers. In applying this approach to breast cancer one potential challenge is the disease's considerable heterogeneity. Triple-negative (TN) breast cancer is a particularly lethal breast cancer subtype that is known to have a unique biology. Consequently, there is a clinical need to discover early detection biomarkers for TN disease, and such biomarkers may be more readily identifiable given the more aggressive nature and growth patterns of these tumors. Objective: To discover and initially validate novel TN breast cancer specific early detection biomarkers using preclinical plasma samples. Methods: We conducted a nested case-control study of TN breast cancer within the Women's Health Initiative (WHI) Observational Study (OS) consisting of 28 TN cases whose blood was drawn 17 months prior to their breast cancer diagnosis and an equal number of matched controls. The 28 matched sets were equally divided into a training set, used for discovery, and an independent test set, used for validation, and interrogated using a customized antibody microarray. Results: In the training set, of the 915 antibodies assessed, 55 (6.0%) were statistically significantly different between cases and controls at p<0.05 and in the test set 128 (14.0%) were statistically different. Of the 55 candidates identified in the training set, 15 were validated in the test set at p<0.05. Of these 15 candidates, 13 had higher levels in cases compared to controls. The candidates with the strongest signals included myosin-5A (log2 ratio=1.26), arfaptin-2 (log2 ratio=1.02), integrin-beta1 (log2 ratio=0.99), phosphoserine aminotransferase (log2 ratio=0.94), beta-catenin (log2 ratio=0.92), mast/stem cell growth factor receptor (log2 ratio=0.90), and IGFBP-2 (log2 ratio=−1.18). Conclusions: Several unique, novel candidate early detection biomarkers specific to TN breast cancer were discovered and initially validated in preclinical samples. These findings warrant validation in additional sets of TN cases and controls to further evaluate their potential clinical significance. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 690. doi:1538-7445.AM2012-690
Published Version
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