DNA methylation markers for breast cancer detection in the developing world

Bradley M. Downs, Claudia Mercado-Rodriguez, Ashley Cimino-Mathews, Chuang Chen, Jing Ping Yuan, Eunice Van Den Berg, Leslie M. Cope, Fernando Schmitt, Gary M. Tse, Syed Z. Ali, Danielle Meir-Levi, Rupali Sood, Juanjuan Li, Andrea L. Richardson, Marina B. Mosunjac, Monica Rizzo, Suzana Tulac, Kriszten J. Kocmond, Timothy De Guzman, Edwin W. LaiBrian Rhees, Michael Bates, Antonio C. Wolff, Edward Gabrielson, Susan C. Harvey, Christopher B. Umbricht, Kala Visvanathan, Mary Jo Fackler, Saraswati Sukumar

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Purpose: An unmet need in low-resource countries is an automated breast cancer detection assay to prioritize women who should undergo core breast biopsy and pathologic review. 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). Experimental Design: Two case-control 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. Results: 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- 0.970). In the FNA pilot, we achieved an AUC of 0.960 (95% CI = 0.883-1.0) using the automated cartridge system. Conclusions: We developed and piloted a fast and accurate methylation marker-based 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.

Original languageEnglish (US)
Pages (from-to)6357-6367
Number of pages11
JournalClinical Cancer Research
Issue number21
StatePublished - Nov 1 2019

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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