Circulating microRNAs as Surrogate Markers for Circulating Tumour Cells and Prognostic Markers in Metastatic Breast Cancer

Purpose: The utility of circulating tumour cells (CTCs) as a prognostic marker in metastatic breast cancer (MBC) has been well-established. However, their efficacy and accuracy are still under scrutiny mainly due to methods of their enrichment and identification. We hypothesized that circulating microRNAs (miRNAs) can predict the CTC status of MBC patients, and tested for the same. Furthermore, we aimed at establishing a panel of circulating miRNAs capable of differentiating MBC cases from healthy controls. Experimental design: Circulating miRNAs from plasma of CTC-positive and CTC-negative MBC patients, and healthy controls were profiled by TaqMan Human MicroRNA arrays. Candidates from the initial screen were validated in an extended cohort of 269 individuals (61 CTC-positive, 72 CTCnegative, 60 CTC-low MBC cases and 76 controls). Results: CTC-positive had significantly higher levels of miR-141, miR-200a, miR-200b, miR-200c, miR203, miR-210, miR-375 and miR-801 than CTC-negative MBC and controls (P < 0.00001), while miR768-3p was present in lower amounts in MBC cases (P < 0.05). miR-200b was singled out as the best marker for distinguishing CTC-positive from CTC-negative patients (AUC 0.88). We identified combinations of miRNAs for differentiating MBC cases from controls (AUC 0.95 for CTC-positive; AUC 0.78 for CTC-negative). Combinations of miRNAs and miR-200b alone were found to be promising prognostic marker for progression-free and overall survival. Conclusion: This is the first study to document the capacity of circulating miRNAs to indicate CTC status and their potential as prognostic markers in MBC patients. Research. on October 17, 2017. © 2012 American Association for Cancer clincancerres.aacrjournals.org Downloaded from Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 4, 2012; DOI: 10.1158/1078-0432.CCR-12-1407