Total circulating microRNA level as an independent prognostic marker for risk stratification in breast cancer

Abstract

Abstract Background Although breast cancer (BC) has a high survival rate, relapse events may occur which ultimately lead to aggressive disease. Circulating cell-free microRNAs (cf-miRNAs) are a promising minimally invasive biomarker with diagnostic and/or prognostic potential. Unfortunately, there is still no consensus as to a universal cf-miRNA biomarker in BC and there has been no clinical implementation until now. One major limitation is the technical variation with cf-miRNA isolation and specific quantification methods. Methods In this study, we assessed the total levels of cf-miRNAs as a potential prognostic marker for BC in 356 plasma samples from 250 BC patients. Results High levels of cf-miRNAs significantly correlated with unfavourable clinical features including tumour stage, load and the presence of metastasis at diagnosis. With more than 9 years of follow-up, we could show that global cf-miRNA levels significantly correlated with cancer relapse which was confirmed in multivariate cox regression analysis. Finally, for a subset of patients where the serial plasma was available, levels of cf-miRNAs increased in the plasma prior to clinical detection of progressive disease and were massively elevated in patients who died compared to those still alive at the last timepoint of measurement. Conclusions This is the first study to suggest that total cf-miRNA levels in the blood can be used as an independent prognostic marker for BC.