The expression of microRNAs (miRNAs) in a tissue- and development-specific manner has indicated that they play an essential role in the maintenance of biological homeostasis. In cancer, the deregulation of these small non-coding RNA molecules modulates the expression of numerous tumor-associated genes and cellular processes. The high levels of cancer-associated sensitivity and specificity of plasma/serum and exosomal miRNA profiles reflect disease development, tumor load, malignant progression towards metastatic relapse and drug resistance. The present review focuses on the findings related to the expression and function of miRNAs in breast cancer, and discusses the potential clinical uses of miRNAs, including their roles as therapeutic targets and diagnostic markers.

Strehl JD, Wachter DL, Fasching PA, et al.: Invasive breast cancer: Recognition of molecular subtypes. Breast Care (Basel) 2011;6:258-264.
Pritchard KI: Endocrine therapy: Is the first generation of targeted drugs the last? J Intern Med 2013;274:144-152.
Krol J, Loedige I, Filipowicz W: The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 2010;11:597-610.
Bartel DP: MicroRNAs: Target recognition and regulatory functions. Cell 2009;136:215-233.
Höck J, Meister G: The Argonaute protein family. Genome Biol 2008;9:210.
Calin GA, Sevignani C, Dumitru CD, et al.: Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA 2004;101:2999-3004.
Schwarzenbach H, Nishida N, Calin GA, Pantel K: Clinical relevance of circulating cell-free microRNAs in cancer. Nat Rev Clin Oncol 2014;11:145-156.
Schwarzenbach H: The clinical relevance of circulating, exosomal miRNAs as biomarkers for cancer. Expert Rev Mol Diagn 2015;15:1159-1169.
Lee TH, D'Asti E, Magnus N, et al.: Microvesicles as mediators of intercellular communication in cancer-the emerging science of cellular ‘debris'. Semin Immunopathol 2011;33:455-467.
Valadi H, Ekstrom K, Bossios A, et al.: Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007;9:654-659.
Zhao L, Liu W, Xiao J, Cao B: The role of exosomes and ‘exosomal shuttle microRNA' in tumorigenesis and drug resistance. Cancer Lett 2015;356:339-346.
Igaz I, Igaz P: Tumor surveillance by circulating microRNAs: A hypothesis. Cell Mol Life Sci 2014;71:4081-4087.
Azmi AS, Bao B, Sarkar FH: Exosomes in cancer development, metastasis, and drug resistance: A comprehensive review. Cancer Metastasis Rev 2013;32:623-642.
Ostenfeld MS, Jeppesen DK, Laurberg JR, et al.: Cellular disposal of miR23b by RAB27-dependent exosome release is linked to acquisition of metastatic properties. Cancer Res 2014;74:5758-5771.
Zhou W, Fong MY, Min Y, et al.: Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis. Cancer Cell 2014;25:501-515.
Chen WX, Zhong SL, Ji MH, et al.: MicroRNAs delivered by extracellular vesicles: An emerging resistance mechanism for breast cancer. Tumour Biol 2014;35:2883-2892.
Chen WX, Liu XM, Lv MM, et al.: Exosomes from drug-resistant breast cancer cells transmit chemoresistance by a horizontal transfer of microRNAs. PloS One 2014;9:e95240.
Chen C, Ridzon DA, Broomer AJ, et al.: Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res 2005;33:e179.
Chugh P, Dittmer DP: Potential pitfalls in microRNA profiling. Wiley Interdiscip Rev RNA 2012;3:601-616.
Schwarzenbach H, Machado da Silva A, Calin G, Pantel K: Data normalization strategies for microRNA quantification. Clin Chem 2015;61:1333-1342.
Silveri L, Tilly G, Vilotte JL, Le Provost F: MicroRNA involvement in mammary gland development and breast cancer. Reprod Nutr Dev 2006;46:549-556.
Zhu J, Zheng Z, Wang J, et al.: Different miRNA expression profiles between human breast cancer tumors and serum. Front Genet 2014;5:149.
Ma L, Teruya-Feldstein J, Weinberg RA: Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 2007;449:682-688.
Anfossi S, Giordano A, Gao H, et al.: High serum miR-19a levels are associated with inflammatory breast cancer and are predictive of favorable clinical outcome in patients with metastatic HER2(+) inflammatory breast cancer. PloS One 2014;9:e83113.
Gee HE, Camps C, Buffa FM, et al.: MicroRNA-10b and breast cancer metastasis. Nature 2008;455:E8-9; author reply E9.
Eichelser C, Flesch-Janys D, Chang-Claude J, et al.: Deregulated serum concentrations of circulating cell-free microRNAs miR-17, miR-34a, miR-155, and miR-373 in human breast cancer development and progression. Clin Chem 2013;59:1489-1496.
Schwarzenbach H: Circulating nucleic acids as biomarkers in breast cancer. Breast Cancer Res 2013;15:211.
Markou A, Zavridou M, Sourvinou I, et al.: Direct comparison of metastasis-related miRNAs expression levels in circulating tumor cells, corresponding plasma, and primary tumors of breast cancer patients. Clin Chem 2016;62:1002-1011.
Gao J, Zhang Q, Xu J, et al.: Clinical significance of serum miR-21 in breast cancer compared with CA153 and CEA. Chin J Cancer Res 2013;25:743-748.
Wang F, Hou J, Jin W, et al.: Increased circulating microRNA-155 as a potential biomarker for breast cancer screening: A meta-analysis. Molecules 2014;19:6282-6293.
Taslim C, Weng DY, Brasky TM, et al.: Discovery and replication of microRNAs for breast cancer risk using genome-wide profiling. Oncotarget 2016;7:86457-86468.
Toraih EA, Mohammed EA, Farrag S, et al.: Pilot study of serum microRNA-21 as a diagnostic and prognostic biomarker in Egyptian breast cancer patients. Mol Diagn Ther 2015;19:179-190.
Rigaud VO, Ferreira LR, Ayub-Ferreira SM, et al.: Circulating miR-1 as a potential biomarker of doxorubicin-induced cardiotoxicity in breast cancer patients. Oncotarget 2017;8:6994-7002.
Kleivi Sahlberg K, Bottai G, Naume B, et al.: A serum microRNA signature predicts tumor relapse and survival in triple-negative breast cancer patients. Clin Cancer Res 2015;21:1207-1214.
Muller V, Gade S, Steinbach B, et al.: Changes in serum levels of miR-21, miR-210, and miR-373 in HER2-positive breast cancer patients undergoing neoadjuvant therapy: A translational research project within the Geparquinto trial. Breast cancer Res Treat 2014;147:61-68.
Wang G, Wang L, Sun S, et al.: Quantitative measurement of serum microRNA-21 expression in relation to breast cancer metastasis in Chinese females. Ann Lab Med 2015;35:226-232.
Zhao R, Wu J, Jia W, et al.: Plasma miR-221 as a predictive biomarker for chemoresistance in breast cancer patients who previously received neoadjuvant chemotherapy. Onkologie 2011;34:675-680.
Wang H, Tan G, Dong L, et al.: Circulating MiR-125b as a marker predicting chemoresistance in breast cancer. PloS One 2012;7:e34210.
Li Q, Liu M, Ma F, et al.: Circulating miR-19a and miR-205 in serum may predict the sensitivity of luminal A subtype of breast cancer patients to neoadjuvant chemotherapy with epirubicin plus paclitaxel. PloS One 2014;9:e104870.
Wu X, Somlo G, Yu Y, et al.: De novo sequencing of circulating miRNAs identifies novel markers predicting clinical outcome of locally advanced breast cancer. J Transl Med 2012;10:42.
Yadav P, Mirza M, Nandi K, et al.: Serum microRNA-21 expression as a prognostic and therapeutic biomarker for breast cancer patients. Tumour Biol 2016;37:15275-15282.
Gu X, Xue JQ, Han SJ, et al.: Circulating microRNA-451 as a predictor of resistance to neoadjuvant chemotherapy in breast cancer. Cancer Biomark 2016;16:395-403.
Melo SA, Sugimoto H, O'Connell JT, et al.: Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis. Cancer Cell 2014;26:707-721.
Hannafon BN, Trigoso YD, Calloway CL, et al.: Plasma exosome microRNAs are indicative of breast cancer. Breast Cancer Res 2016;18:90.
Eichelser C, Stuckrath I, Muller V, et al.: Increased serum levels of circulating exosomal microRNA-373 in receptor-negative breast cancer patients. Oncotarget 2014;5:9650-9663.
Monroig Pdel C, Chen L, Zhang S, Calin GA: Small molecule compounds targeting miRNAs for cancer therapy. Adv Drug Deliv Rev 2015;81:104-116.
Lin Z, Li JW, Wang Y, et al.: Abnormal miRNA-30e expression is associated with breast cancer progression. Clin Lab 2016;62:121-128.
Chen W, Cai F, Zhang B, et al.: The level of circulating miRNA-10b and miRNA-373 in detecting lymph node metastasis of breast cancer: potential biomarkers. Tumour Biol 2013;34:455-462.
Lu Z, Ye Y, Jiao D, et al.: miR-155 and miR-31 are differentially expressed in breast cancer patients and are correlated with the estrogen receptor and progesterone receptor status. Oncology Lett 2012;4:1027-1032.
Matamala N, Vargas MT, Gonzalez-Campora R, et al.: Tumor microRNA expression profiling identifies circulating microRNAs for early breast cancer detection. Clin Chem 2015;61:1098-1106.
Ren GB, Wang L, Zhang FH, et al.: Study on the relationship between miR-520g and the development of breast cancer. Eur Rev Med Pharmacol Sci 2016;20:657-663.
Zeng RC, Zhang W, Yan XQ, et al.: Down-regulation of miRNA-30a in human plasma is a novel marker for breast cancer. Med Oncol 2013;30:477.
Shen J, Hu Q, Schrauder M, et al.: Circulating miR-148b and miR-133a as biomarkers for breast cancer detection. Oncotarget 2014;5:5284-5294.
Stückrath I, Rack B, Janni W, et al.: Aberrant plasma levels of circulating miR-16, miR-107, miR-130a and miR-146a are associated with lymph node metastasis and receptor status of breast cancer patients. Oncotarget 2015;6:13387-13401.
Cuk K, Zucknick M, Heil J, et al.: Circulating microRNAs in plasma as early detection markers for breast cancer. Int J Cancer 2013;132:1602-1612.
Guo LJ, Zhang QY: Decreased serum miR-181a is a potential new tool for breast cancer screening. Int J Mol Med 2012;30:680-686.
Madhavan D, Zucknick M, Wallwiener M, et al.: Circulating miRNAs as surrogate markers for circulating tumor cells and prognostic markers in metastatic breast cancer. Clin Cancer Res 2012;18:5972-5982.
Ng EK, Li R, Shin VY, et al.: Circulating microRNAs as specific biomarkers for breast cancer detection. PloS One 2013;8:e53141.
Cuk K, Zucknick M, Madhavan D, et al.: Plasma microRNA panel for minimally invasive detection of breast cancer. PloS One 2013;8:e76729.
Shin VY, Siu JM, Cheuk I, et al.: Circulating cell-free miRNAs as biomarker for triple-negative breast cancer. Br J Cancer 2015;112:1751-1759.
Zhang H, Li B, Zhao H, Chang J: The expression and clinical significance of serum miR-205 for breast cancer and its role in detection of human cancers. Int J Clin Exp Med 2015;8:3034-3043.
Wang F, Zheng Z, Guo J, Ding X: Correlation and quantitation of microRNA aberrant expression in tissues and sera from patients with breast tumor. Gynecol Oncol 2010;119:586-593.
Mangolini A, Ferracin M, Zanzi MV, et al.: Diagnostic and prognostic microRNAs in the serum of breast cancer patients measured by droplet digital PCR. Biomark Res 2015;3:12.
Luo J, Zhao Q, Zhang W, et al.: A novel panel of microRNAs provides a sensitive and specific tool for the diagnosis of breast cancer. Mol Med Rep 2014;10:785-791.
Mar-Aguilar F, Mendoza-Ramirez JA, Malagon-Santiago I, et al.: Serum circulating microRNA profiling for identification of potential breast cancer biomarkers. Dis Markers 2013;34:163-169.
Sochor M, Basova P, Pesta M, et al.: Oncogenic microRNAs: miR-155, miR-19a, miR-181b, and miR-24 enable monitoring of early breast cancer in serum. BMC Cancer 2014;14:448.
van Schooneveld E, Wouters MC, Van der Auwera I, et al.: Expression profiling of cancerous and normal breast tissues identifies microRNAs that are differentially expressed in serum from patients with (metastatic) breast cancer and healthy volunteers. Breast Cancer Res 2012;14:R34.
Zhang L, Xu Y, Jin X, et al.: A circulating miRNA signature as a diagnostic biomarker for non-invasive early detection of breast cancer. Breast Cancer Res Treat 2015;154:423-434.
Waters PS, Dwyer RM, Brougham C, et al.: Impact of tumour epithelial subtype on circulating microRNAs in breast cancer patients. PloS One 2014;9:e90605.
Roth C, Rack B, Muller V, et al.: Circulating micro RNAs as blood-based markers for patients with primary and metastatic breast cancer. Breast Cancer Res 2010;12:R90.
Li XX, Gao SY, Wang PY, et al.: Reduced expression levels of let-7c in human breast cancer patients. Oncology Lett 2015;9:1207-1212.
Shaker O, Maher M, Nassar Y, et al.: Role of micro RNAs -29b-2, -155, -197 and -205 as diagnostic biomarkers in serum of breast cancer females. Gene 2015;560:77-82.
Fu L, Li Z, Zhu J, et al.: Serum expression levels of microRNA-382-3p, -598-3p, -1246 and -184 in breast cancer patients. Oncology Lett 2016;12:269-274.
Ferracin M, Lupini L, Salamon I, et al.: Absolute quantification of cell-free microRNAs in cancer patients. Oncotarget 2015;6:14545-14555.
Si H, Sun X, Chen Y, et al.: Circulating microRNA-92a and microRNA-21 as novel minimally invasive biomarkers for primary breast cancer. J Cancer Res Clin Oncol 2013;139:223-229.
Schwarzenbach H, Milde-Langosch K, Steinbach B, et al.: Diagnostic potential of PTEN-targeting miR-214 in the blood of breast cancer patients. Breast Cancer Res Treat 2012;134:933-941.
Asaga S, Kuo C, Nguyen T, et al.: Direct serum assay for microRNA-21 concentrations in early and advanced breast cancer. Clin Chem 2011;57:84-91.
Sun Y, Wang M, Lin G, et al.: Serum microRNA-155 as a potential biomarker to track disease in breast cancer. PloS One 2012;7:e47003.
Kodahl AR, Lyng MB, Binder H, et al.: Novel circulating microRNA signature as a potential non-invasive multi-marker test in ER-positive early-stage breast cancer: A case control study. Mol Oncol 2014;8:874-883.
Zhao FL, Hu GD, Wang XF, et al.: Serum overexpression of microRNA-10b in patients with bone metastatic primary breast cancer. J Int Med Res 2012;40:859-866.
Hu Z, Dong J, Wang LE, et al.: Serum microRNA profiling and breast cancer risk: The use of miR-484/191 as endogenous controls. Carcinogenesis 2012;33:828-834.
Chan M, Liaw CS, Ji SM, et al.: Identification of circulating microRNA signatures for breast cancer detection. Clinical Cancer Res 2013;19:4477-4487.
Zearo S, Kim E, Zhu Y, et al.: MicroRNA-484 is more highly expressed in serum of early breast cancer patients compared to healthy volunteers. BMC Cancer 2014;14:200.
Tang D, Zhang Q, Zhao S, et al.: The expression and clinical significance of microRNA-1258 and heparanase in human breast cancer. Clin Biochem 2013;46:926-932.
Zhao FL, Dou YC, Wang XF, et al.: Serum microRNA-195 is down-regulated in breast cancer: A potential marker for the diagnosis of breast cancer. Mol Biol Rep 2014;41:5913-5922.
Shimomura A, Shiino S, Kawauchi J, et al.: Novel combination of serum microRNA for detecting breast cancer in the early stage. Cancer Sci 2016;107:326-334.
Zheng R, Pan L, Gao J, et al.: Prognostic value of miR-106b expression in breast cancer patients. J Surg Res 2015;195:158-165.
Li J, Song ZJ, Wang YY, et al.: Low levels of serum miR-99a is a predictor of poor prognosis in breast cancer. Genet Mol Res 2016;15.
Joosse SA, Muller V, Steinbach B, et al.: Circulating cell-free cancer-testis MAGE-A RNA, BORIS RNA, let-7b and miR-202 in the blood of patients with breast cancer and benign breast diseases. Br J Cancer 2014;111:909-917.
Hsieh TH, Hsu CY, Tsai CF, et al.: miR-125a-5p is a prognostic biomarker that targets HDAC4 to suppress breast tumorigenesis. Oncotarget 2015;6:494-509.
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