C distribution, thus providing evidence that this set of DNA methylation biomarkers will likely generalize to prospective patient samples. Keywords: DNA methylation, Breast cancer, ER/PR hormone receptor statusBackground Breast cancer has traditionally been described by histopathological staging based on size, degree of invasiveness, and lymph node metastasis and by immunochemical analysis of the epidermal growth factor receptor HER2 and the estrogen (ER) and progesterone (PR) receptors. Recently, there has been an increased awareness of the potential* Correspondence: [email protected]; [email protected] 1 Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago (UIC), M/C 669900 S. Ashland Ave., Chicago 60607IL, USA 5 Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago (UIC), M/C 923, Chicago 60612IL, USA Full list of author information is available at the end of the articleinfluence of socioeconomic and psychosocial factors on breast cancer aggressiveness characteristics [1?]. One mechanism by which these processes might exert their effects on activity of breast cancer genes is through epigenetic alterations, including DNA methylation. Therefore, addition of classification based on DNA methylation and gene expression might improve prognostic prediction to therapeutic response or survival. Previous studies using established cancer cell models showed that tumor evolution includes genome-wide loss of DNA methylation (hypomethylation) as well as increase in promoter methylation at CpG islands?2016 Benevolenskaya et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Benevolenskaya et al. Clinical Epigenetics (2016) 8:Page 2 of(promoter hypermethylation) . Genes involved in specific biological pathways have been recognized to be methylated at their promoters in various types of cancer, including breast cancer . Distinctive patterns of promoter methylation have been reported previously for ER/PR-positive versus ER/PR-negative tumors [8?0]. ER/PR-negative tumors are of particular interest because they tend to be the most aggressive form PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27607577 and lack targets for hormone therapy. Therefore, these new DNA methylation-based characteristics had a potential to contribute prognostic value in breast cancer management. Prior studies using panels of DNA methylation markers, however, are plagued by lack of reproducibility, in part because these studies tend to focus on the top-most performing markers , as opposed to genome-wide association. The reproducibility was likely varied from study to study due to random error associated with commonly used small sample size. The prevalence of certain markers in particular cohort populations was not taken into HS-173MedChemExpress HS-173 account, as race and ethnicity were either not reported or lacking Hispanic and African-American patient population [8?0, 12]. The aims of our analyses were (1) to identify a set of g.