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Therefore, we sought to identify and validate a panel of methylated DNA markers to discriminate between cancer and benign breast lesions using cells obtained by fine-needle aspiration (FNA).<\/jats:p><jats:p>Experimental Design: Two case\u2013control studies were conducted comparing cancer and benign breast tissue identified from clinical repositories in the United States, China, and South Africa for marker selection\/training (N = 226) and testing (N = 246). Twenty-five methylated markers were assayed by Quantitative Multiplex-Methylation-Specific PCR (QM-MSP) to select and test a cancer-specific panel. Next, a pilot study was conducted on archival FNAs (49 benign, 24 invasive) from women with mammographically suspicious lesions using a newly developed, 5-hour, quantitative, automated cartridge system. We calculated sensitivity, specificity, and area under the receiver-operating characteristic curve (AUC) compared with histopathology for the marker panel.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>In the discovery cohort, 10 of 25 markers were selected that were highly methylated in breast cancer compared with benign tissues by QM-MSP. In the independent test cohort, this panel yielded an AUC of 0.937 (95% CI = 0.900\u20130.970). In the FNA pilot, we achieved an AUC of 0.960 (95% CI = 0.883\u20131.0) using the automated cartridge system.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions:<\/jats:title><jats:p>We developed and piloted a fast and accurate methylation marker\u2013based automated cartridge system to detect breast cancer in FNA samples. This quick ancillary test has the potential to prioritize cancer over benign tissues for expedited pathologic evaluation in poorly resourced countries.<\/jats:p><\/jats:sec>","DOI":"10.1158\/1078-0432.ccr-18-3277","type":"journal-article","created":{"date-parts":[[2019,7,12]],"date-time":"2019-07-12T23:19:26Z","timestamp":1562973566000},"page":"6357-6367","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["DNA Methylation Markers for Breast Cancer Detection in the Developing World"],"prefix":"10.1158","volume":"25","author":[{"given":"Bradley M.","family":"Downs","sequence":"first","affiliation":[{"name":"1Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland."}]},{"given":"Claudia","family":"Mercado-Rodriguez","sequence":"additional","affiliation":[{"name":"1Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland."}]},{"given":"Ashley","family":"Cimino-Mathews","sequence":"additional","affiliation":[{"name":"2Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland."}]},{"given":"Chuang","family":"Chen","sequence":"additional","affiliation":[{"name":"3Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, P.R. China."}]},{"given":"Jing-Ping","family":"Yuan","sequence":"additional","affiliation":[{"name":"4Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, P.R. China."}]},{"given":"Eunice","family":"Van Den Berg","sequence":"additional","affiliation":[{"name":"5Department of Anatomical Pathology, University of Witwaterstrand and National Health Laboratory Service, Johannesburg, South Africa."}]},{"given":"Leslie M.","family":"Cope","sequence":"additional","affiliation":[{"name":"1Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3711-8681","authenticated-orcid":false,"given":"Fernando","family":"Schmitt","sequence":"additional","affiliation":[{"name":"6Medical Faculty of Porto University, Institute of Molecular Pathology and Immunology of Porto University, Porto, Portugal."}]},{"given":"Gary M.","family":"Tse","sequence":"additional","affiliation":[{"name":"7Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region."}]},{"given":"Syed Z.","family":"Ali","sequence":"additional","affiliation":[{"name":"2Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland."}]},{"given":"Danielle","family":"Meir-Levi","sequence":"additional","affiliation":[{"name":"1Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland."}]},{"given":"Rupali","family":"Sood","sequence":"additional","affiliation":[{"name":"1Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland."}]},{"given":"Juanjuan","family":"Li","sequence":"additional","affiliation":[{"name":"1Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland."},{"name":"3Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, P.R. China."}]},{"given":"Andrea L.","family":"Richardson","sequence":"additional","affiliation":[{"name":"2Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland."}]},{"given":"Marina B.","family":"Mosunjac","sequence":"additional","affiliation":[{"name":"8Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia."}]},{"given":"Monica","family":"Rizzo","sequence":"additional","affiliation":[{"name":"9Department of Surgery, Emory University School of Medicine, Atlanta, Georgia."}]},{"given":"Suzana","family":"Tulac","sequence":"additional","affiliation":[{"name":"10Cepheid, Sunnyvale, California."}]},{"given":"Kriszten J.","family":"Kocmond","sequence":"additional","affiliation":[{"name":"10Cepheid, Sunnyvale, California."}]},{"given":"Timothy","family":"de Guzman","sequence":"additional","affiliation":[{"name":"10Cepheid, Sunnyvale, California."}]},{"given":"Edwin W.","family":"Lai","sequence":"additional","affiliation":[{"name":"10Cepheid, Sunnyvale, California."}]},{"given":"Brian","family":"Rhees","sequence":"additional","affiliation":[{"name":"10Cepheid, Sunnyvale, California."}]},{"given":"Michael","family":"Bates","sequence":"additional","affiliation":[{"name":"10Cepheid, Sunnyvale, California."}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3734-1063","authenticated-orcid":false,"given":"Antonio C.","family":"Wolff","sequence":"additional","affiliation":[{"name":"1Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland."}]},{"given":"Edward","family":"Gabrielson","sequence":"additional","affiliation":[{"name":"2Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland."}]},{"given":"Susan C.","family":"Harvey","sequence":"additional","affiliation":[{"name":"11Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1993-0553","authenticated-orcid":false,"given":"Christopher B.","family":"Umbricht","sequence":"additional","affiliation":[{"name":"2Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland."},{"name":"12Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland."}]},{"given":"Kala","family":"Visvanathan","sequence":"additional","affiliation":[{"name":"1Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland."},{"name":"13Bloomberg School of Public Health, Baltimore, Maryland."}]},{"given":"Mary Jo","family":"Fackler","sequence":"additional","affiliation":[{"name":"1Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland."}]},{"given":"Saraswati","family":"Sukumar","sequence":"additional","affiliation":[{"name":"1Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, 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