In the current study, we identified four miRNAs with dysregulated expression in the circulation of women with Luminal A-like breast cancer. MiR-181a and miR-652 were downregulated in Luminal A-like breast tumor tissue, while miR-29a was not. These findings support the hypothesis that circulating miRNA expression profiles may not act as a direct window on tumor activity and brings into question the mechanism by which they enter the blood stream, in addition to their functional role, if any, in the peripheral circulation. These processes remain poorly understood. MiRNAs can enter the peripheral circulation following selective secretion from tumor cells or circulating micro-vesicles. Other cells in the tumor microenvironment can also secrete miRNAs. Meanwhile another school of thought suggests that miRNAs may be detectable in the circulation as a consequence of passive leakage from apoptotic and necrotic cells. In reality it is likely that both of these theories are true, with accumulating evidence to support both plausible proposals. Once in the circulation, miRNA transport is not uniform. Some miRNAs are encapsulated in microvesicles, apoptotic bodies, exosomes or high-density lipoprotein particles while others are in combination with proteins of the Argonaute family. The protection conveyed by microparticles or in combination with AGO proteins explains the stability of miRNAs in nuclease rich and protease rich environments, such as the circulation, when compared to mRNA. The majority of circulating miRNAs, as much as 90–95%, are transported in combination with the AGO protein family. The functional role of miRNAs in circulation has yet to be fully elucidated; are these tiny particles merely secreted as by-products of physiological and BU 4061T pathological processes or are they circulating messengers, with important intercellular and inter-organ cell to cell messaging capabilities? Some recent studies allude to the potential for exosomally-packaged miRNA to act as cell to cell signaling molecules, during viral infection, the immune response and most significantly cancer progression. However, despite these reports, it is likely that the majority of circulating extracellular miRNAs, particularly the AGO-transported form, have no functional role. Nonetheless, regardless of their source, their presence, relative stability and ease of detection can be exploited for biomarker means. In this study ANN identified four specific miRNAs as being significantly altered in the circulation of women with Luminal Alike breast cancer. ANN data-mining algorithms have been shown to provide a robust solution to issues encountered within miRNA array data. They have been shown to cope with non-linearity, and complexity; whilst offering the ability to identify biomarkers of high biological relevance and good predictive sensitivity and specificity. MiR-181a has previously been reported as being significantly under-expressed in the serum of women with breast cancer compared to healthy controls. It has also been shown to be downregulated in tumor tissue of lung, oral, hepatocellular, and ovarian cancers. In addition, miR-181a was identified as a potential prognostic factor for colorectal and gastric cancer.