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Discovery and preliminary confirmation of novel early detection biomarkers for triple-negative breast cancer using preclinical plasma samples from the Women’s Health Initiative observational study

  • Epidemiology
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Abstract

Triple-negative breast cancer is a particularly aggressive and lethal breast cancer subtype that is more likely to be interval-detected rather than screen-detected. The purpose of this study is to discover and initially validate novel early detection biomarkers for triple-negative breast cancer using preclinical samples. Plasma samples collected up to 17 months before diagnosis from 28 triple-negative cases and 28 matched controls from the Women’s Health Initiative Observational Study were equally divided into a training set and a test set and interrogated by a customized antibody array. Data were available on 889 antibodies; in the training set, statistically significant differences in case versus control signals were observed for 93 (10.5 %) antibodies at p < 0.05. Of these 93 candidates, 29 were confirmed in the test set at p < 0.05. Areas under the curve for these candidates ranged from 0.58 to 0.79. With specificity set at 98 %, sensitivity ranged from 4 to 68 % with 20 candidates having a sensitivity ≥20 % and 6 having a sensitivity ≥40 %. In an analysis of KEGG gene sets, the pyrimidine metabolism gene set was upregulated in cases compared to controls (p = 0.004 in the testing set) and the JAK/Stat signaling pathway gene set was downregulated (p = 0.003 in the testing set). Numerous potential early detection biomarkers specific to triple-negative breast cancer in multiple pathways were identified. Further research is required to followup on promising candidates in larger sample sizes and to better understand their potential biologic importance as our understanding of the etiology of triple-negative breast cancer continues to grow.

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Acknowledgments

This work was supported by the National Cancer Institute (grant number U01-CA152637) and the National Heart Lung and Blood Institute (grant number N01-WH-74313).

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Christopher I. Li, Justin E. Mirus, Yuzheng Zhang, Arturo B. Ramirez, Jon J. Ladd, Ross L. Prentice, Martin W. McIntosh, Samir M. Hanash & Paul D. Lampe

  2. Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., M4-C308, P.O. Box 19024, Seattle, WA, 98109-1024, USA

    Christopher I. Li

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  1. Christopher I. Li
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  2. Justin E. Mirus
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Correspondence to Christopher I. Li.

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Li, C.I., Mirus, J.E., Zhang, Y. et al. Discovery and preliminary confirmation of novel early detection biomarkers for triple-negative breast cancer using preclinical plasma samples from the Women’s Health Initiative observational study. Breast Cancer Res Treat 135, 611–618 (2012). https://doi.org/10.1007/s10549-012-2204-4

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  • DOI: https://doi.org/10.1007/s10549-012-2204-4

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