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Advances in liquid biopsy using circulating tumor cells and circulating cell-free tumor DNA for detection and monitoring of breast cancer

  • Xiaofen Zhang
  • Shaoqing Ju
  • Xudong Wang
  • Hui CongEmail author
Review Article
Part of the following topical collections:
  1. Clinical Practice

Abstract

Overview the progress of liquid biopsy using circulating tumor cells (CTCs) and circulating cell-free tumor DNA (cfDNA) to detect and monitor breast cancer. Based on numerous research efforts, the potential value of CTCs and cfDNA in the clinical aspects of cancer has become clear. With the development of next-generation sequencing analysis and newly developed technologies, many technical issues have been resolved, making liquid biopsy widely used in clinical practice. They can be powerful tools for dynamic monitoring of tumor progression and therapeutic efficacy. In the field of breast cancer, liquid biopsy is a research hot spot in recent years, playing a key role in monitoring breast cancer metastasis, predicting disease recurrence and assessing clinical drug resistance. Liquid biopsy has the advantages of noninvasive, high sensitivity, high specificity and real-time dynamic monitoring. Still application is far from reality, but the research and application prospects of CTCs and cfDNA in breast cancer are still worth exploring and discovering. This article reviews the main techniques and applications of CTCs and cfDNA in breast cancer.

Keywords

Circulating tumor cells (CTCs) Circulating cell-free tumor DNA (ctDNA) Breast cancer Liquid biopsy 

Notes

Acknowledgements

This work was supported by the National Basic Research Program of China (973 Program No. 2012CB933303), the National Natural Science Foundation of China (Program Nos. 81472751, 61271162, 61401442 and 61571428), the Shanghai Pujiang Program (No. 15PJ1409800), The Jiangsu Provincial Funds for Six Categories of Top Talents (Program No.WS-066) and The Research project of Jiangsu provincial health and Family Planning Commission (Program No. H201526).

Compliance with ethical standards

Conflict of interest

We have declared that no competing interests exist. The authors alone are responsible for the content and writing of the paper.

Ethical approval

The study complies with the Declaration of Helsinki and was approved by the Ethics Committee of Affiliated Hospital of Nantong University, and all patients gave written informed consent.

References

  1. 1.
    Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66:115–32.CrossRefGoogle Scholar
  2. 2.
    Kim C, Paik S. Gene-expression-based prognostic assays for breast cancer. Nat Rev Clin Oncol. 2010;7:340–7.CrossRefGoogle Scholar
  3. 3.
    Jain RK, Duda DG, Willett CG, Sahani DV, Zhu AX, Loeffler JS, et al. Biomarkers of response and resistance to antiangiogenic therapy. Nat Rev Clin Oncol. 2009;6:327–38.CrossRefGoogle Scholar
  4. 4.
    Bardelli A, Pantel K. Liquid biopsies, what we do not know (yet). Cancer Cell. 2017;31:172–9.CrossRefGoogle Scholar
  5. 5.
    Bonnomet A, Syne L, Brysse A, Feyereisen E, Thompson EW, Noel A, et al. A dynamic in vivo model of epithelial-to-mesenchymal transitions in circulating tumor cells and metastases of breast cancer. Oncogene. 2012;31:3741–53.CrossRefGoogle Scholar
  6. 6.
    Yu M, Bardia A, Aceto N, Bersani F, Madden MW, Donaldson MC, et al. Cancer therapy. Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility. Science. 2014;345:216–20.CrossRefGoogle Scholar
  7. 7.
    Bednarz-Knoll N, Alix-Panabieres C, Pantel K. Plasticity of disseminating cancer cells in patients with epithelial malignancies. Cancer Metastasis Rev. 2012;31:673–87.CrossRefGoogle Scholar
  8. 8.
    Markiewicz A, Nagel A, Szade J, Majewska H, Skokowski J, Seroczynska B, et al. Aggressive phenotype of cells disseminated via hematogenous and lymphatic route in breast cancer patients. Transl Oncol. 2018;11:722–31.CrossRefGoogle Scholar
  9. 9.
    Boulding T, McCuaig RD, Tan A, Hardy K, Wu F, Dunn J, et al. LSD1 activation promotes inducible EMT programs and modulates the tumour microenvironment in breast cancer. Sci Rep. 2018;8:73.CrossRefGoogle Scholar
  10. 10.
    Hou P, Li L, Chen F, Chen Y, Liu H, Li J, et al. PTBP3-mediated regulation of ZEB1 mRNA stability promotes epithelial-mesenchymal transition in breast cancer. Can Res. 2018;78:387–98.CrossRefGoogle Scholar
  11. 11.
    L. N. CTC clusters more likely to cause metastasis. Cancer Discov. 2014;4:1246–7.Google Scholar
  12. 12.
    Giuliano M, Shaikh A, Lo HC, Arpino G, De Placido S, Zhang XH, et al. Perspective on circulating tumor cell clusters: why it takes a village to metastasize. Can Res. 2018;78:845–52.CrossRefGoogle Scholar
  13. 13.
    King MR, Phillips KG, Mitrugno A, Lee TR, de Guillebon AM, Chandrasekaran S, et al. A physical sciences network characterization of circulating tumor cell aggregate transport. Am J Physiol Cell Physiol. 2015;308:792–802.CrossRefGoogle Scholar
  14. 14.
    Allard WJ, Matera J, Miller MC, Repollet M, Connelly MC, Rao C, et al. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res. 2004;10:6897–904.CrossRefGoogle Scholar
  15. 15.
    Riethdorf S, Fritsche H, Muller V, Rau T, Schindlbeck C, Rack B, et al. Detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer: a validation study of the Cell Search system. Clin Cancer Res. 2007;13:920–8.CrossRefGoogle Scholar
  16. 16.
    Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004;351:781–91.CrossRefGoogle Scholar
  17. 17.
    Janni WJ, Rack B, Terstappen LW, Pierga JY, Taran FA, Fehm T, et al. Pooled analysis of the prognostic relevance of circulating tumor cells in primary breast cancer. Clin Cancer Res. 2016;22:2583–93.CrossRefGoogle Scholar
  18. 18.
    Aceto N, Bardia A, Miyamoto DT, Donaldson MC, Wittner BS, Spencer JA, et al. Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell. 2014;158:1110–22.CrossRefGoogle Scholar
  19. 19.
    Ksiazkiewicz M, Markiewicz A, Zaczek AJ. Epithelial-mesenchymal transition: a hallmark in metastasis formation linking circulating tumor cells and cancer stem cells. Pathobiology. 2012;79:195–208.CrossRefGoogle Scholar
  20. 20.
    Karabacak NM, Spuhler PS, Fachin F, Lim EJ, Pai V, Ozkumur E, et al. Microfluidic, marker-free isolation of circulating tumor cells from blood samples. Nat Protoc. 2014;9:694–710.CrossRefGoogle Scholar
  21. 21.
    Huang Q, Wang FB, Yuan CH, He Z, Rao L, Cai B, et al. Gelatin nanoparticle-coated silicon beads for density-selective capture and release of heterogeneous circulating tumor cells with high purity. Theranostics. 2018;8:1624–35.CrossRefGoogle Scholar
  22. 22.
    Sun N, Wang J, Ji L, Hong S, Dong J, Guo Y, et al. A cellular compatible chitosan nanoparticle surface for isolation and in situ culture of rare number CTCs. Small. 2015;11:5444–51.CrossRefGoogle Scholar
  23. 23.
    Sun N, Li X, Wang Z, Zhang R, Wang J, Wang K, et al. A multiscale TiO2 nanorod array for ultrasensitive capture of circulating tumor cells. ACS Appl Mater Interfaces. 2016;8:12638–43.CrossRefGoogle Scholar
  24. 24.
    Kwak B, Lee J, Lee D, Lee K, Kwon O, Kang S, et al. Selective isolation of magnetic nanoparticle-mediated heterogeneity subpopulation of circulating tumor cells using magnetic gradient based microfluidic system. Biosens Bioelectron. 2017;88:153–8.CrossRefGoogle Scholar
  25. 25.
    Ates HC, Ozgur E, Kulah H. Comparative study on antibody immobilization strategies for efficient circulating tumor cell capture. Biointerphases. 2018;13:021001.CrossRefGoogle Scholar
  26. 26.
    Jan YJ, Chen JF, Zhu Y, Lu YT, Chen SH, Chung H, et al. NanoVelcro rare-cell assays for detection and characterization of circulating tumor cells. Adv Drug Deliv Rev. 2018;125:78–93.CrossRefGoogle Scholar
  27. 27.
    Myung JH, Eblan MJ, Caster JM, Park SJ, Poellmann MJ, Wang K, et al. Multivalent binding and biomimetic cell rolling improves the sensitivity and specificity of circulating tumor cell capture. Clin Cancer Res. 2018;24:2539–47.CrossRefGoogle Scholar
  28. 28.
    Sharma S, Zhuang R, Long M, Pavlovic M, Kang Y, Ilyas A, et al. Circulating tumor cell isolation, culture, and downstream molecular analysis. Biotechnol Adv. 2018;36:1063–78.CrossRefGoogle Scholar
  29. 29.
    Chen K, Dopico P, Varillas JI, Zhang J, George TJ, Fan ZH. Integration of lateral filter arrays with immunoaffinity for circulating tumor cell isolation. Angew Chem Int Ed. 2019;58:7606–10.CrossRefGoogle Scholar
  30. 30.
    Kim TH, Wang Y, Oliver CR, Thamm DH, Cooling L, Paoletti C, et al. A temporary indwelling intravascular aphaeretic system for in vivo enrichment of circulating tumor cells. Nat Commun. 2019;10:1478.CrossRefGoogle Scholar
  31. 31.
    Varillas JI, Zhang J, Chen K, Barnes II, Liu C, George TJ, et al. Microfluidic isolation of circulating tumor cells and cancer stem-like cells from patients with pancreatic ductal adenocarcinoma. Theranostics. 2019;9:1417–25.CrossRefGoogle Scholar
  32. 32.
    Au SH, Edd J, Stoddard AE, Wong KHK, Fachin F, Maheswaran S, et al. Microfluidic isolation of circulating tumor cell clusters by size and asymmetry. Sci Rep. 2017;7:2433.CrossRefGoogle Scholar
  33. 33.
    Wang G, Benasutti H, Jones JF, Shi G, Benchimol M, Pingle S, et al. Isolation of Breast cancer CTCs with multitargeted buoyant immunomicrobubbles. Colloids Surf B. 2018;161:200–9.CrossRefGoogle Scholar
  34. 34.
    Sarioglu AF, Aceto N, Kojic N, Donaldson MC, Zeinali M, Hamza B, et al. A microfluidic device for label-free, physical capture of circulating tumor cell clusters. Nat Methods. 2015;12:685–91.CrossRefGoogle Scholar
  35. 35.
    Choi JW, Kim JK, Yang YJ, Kim P, Yoon KH, Yun SH. Urokinase exerts antimetastatic effects by dissociating clusters of circulating tumor cells. Can Res. 2015;75:4474–82.CrossRefGoogle Scholar
  36. 36.
    Wang C, Mu Z, Chervoneva I, Austin L, Ye Z, Rossi G, et al. Longitudinally collected CTCs and CTC-clusters and clinical outcomes of metastatic breast cancer. Breast Cancer Res Treat. 2017;161:83–94.CrossRefGoogle Scholar
  37. 37.
    Mu Z, Wang C, Ye Z, Austin L, Civan J, Hyslop T, et al. Prospective assessment of the prognostic value of circulating tumor cells and their clusters in patients with advanced-stage breast cancer. Breast Cancer Res Treat. 2015;154:563–71.CrossRefGoogle Scholar
  38. 38.
    Jansson S, Bendahl PO, Larsson AM, Aaltonen KE, Ryden L. Prognostic impact of circulating tumor cell apoptosis and clusters in serial blood samples from patients with metastatic breast cancer in a prospective observational cohort. BMC Cancer. 2016;16:433.CrossRefGoogle Scholar
  39. 39.
    Gkountela S, Castro-Giner F, Szczerba BM, Vetter M, Landin J, Scherrer R, et al. Circulating tumor cell clustering shapes DNA methylation to enable metastasis seeding. Cell. 2019;176:98-112.e14.CrossRefGoogle Scholar
  40. 40.
    Rosenberg R, Gertler R, Friederichs J, Fuehrer K, Dahm M, Phelps R, et al. Comparison of two density gradient centrifugation systems for the enrichment of disseminated tumor cells in blood. Cytometry. 2002;49:150–8.CrossRefGoogle Scholar
  41. 41.
    Jakabova A, Bielcikova Z, Pospisilova E, Matkowski R, Szynglarewicz B, Staszek-Szewczyk U, et al. Molecular characterization and heterogeneity of circulating tumor cells in breast cancer. Breast Cancer Treat. 2017;166:695–700.CrossRefGoogle Scholar
  42. 42.
    Sun N, Li X, Wang Z, Li Y, Pei R. High-purity capture of CTCs based on micro-beads enhanced isolation by size of epithelial tumor cells (ISET) method. Biosens Bioelectron. 2018;102:157–63.CrossRefGoogle Scholar
  43. 43.
    Kobayashi M, Kim SH, Nakamura H, Kaneda S, Fujii T. Cancer cell analyses at the single cell-level using electroactive microwell array device. PLoS ONE. 2015;10:e0139980.CrossRefGoogle Scholar
  44. 44.
    Nguyen NV, Jen CP. Impedance detection integrated with dielectrophoresis enrichment platform for lung circulating tumor cells in a microfluidic channel. Biosens Bioelectron. 2018;121:10–8.CrossRefGoogle Scholar
  45. 45.
    Mostert B, Sleijfer S, Foekens JA, Gratama JW. Circulating tumor cells (CTCs): detection methods and their clinical relevance in breast cancer. Cancer Treat Rev. 2009;35:463–74.CrossRefGoogle Scholar
  46. 46.
    Olsson E, Winter C, George A, Chen Y, Howlin J, Tang MH, et al. Serial monitoring of circulating tumor DNA in patients with primary breast cancer for detection of occult metastatic disease. EMBO Mol Med. 2015;7:1034–47.CrossRefGoogle Scholar
  47. 47.
    Yao X, Choudhury AD, Yamanaka YJ, Adalsteinsson VA, Gierahn TM, Williamson CA, et al. Functional analysis of single cells identifies a rare subset of circulating tumor cells with malignant traits. Integr Biol. 2014;6:388–98.CrossRefGoogle Scholar
  48. 48.
    Zhang L, Ridgway LD, Wetzel MD, Ngo J, Yin W, Kumar D, et al. The identification and characterization of breast cancer CTCs competent for brain metastasis. Sci Transl Med. 2013;5:180ra48.CrossRefGoogle Scholar
  49. 49.
    Maheswaran S, Haber DA. Ex vivo culture of CTCs: an emerging resource to guide cancer therapy. Can Res. 2015;75:2411–5.CrossRefGoogle Scholar
  50. 50.
    Gao D, Vela I, Sboner A, Iaquinta PJ, Karthaus WR, Gopalan A, et al. Organoid cultures derived from patients with advanced prostate cancer. Cell. 2014;159:176–87.CrossRefGoogle Scholar
  51. 51.
    Khoo BL, Grenci G, Jing T, Lim YB, Lee SC, Thiery JP, et al. Liquid biopsy and therapeutic response: circulating tumor cell cultures for evaluation of anticancer treatment. Sci Adv. 2016;2:e1600274.CrossRefGoogle Scholar
  52. 52.
    Wu WJ, Wang ZH, Wang Z, Deng YL, Shi QH. Fast isolation and ex vivo culture of circulating tumor cells from the peripheral blood of lung cancer patients. Hereditas. 2017;39:66–74.Google Scholar
  53. 53.
    Sobral-Filho RG, DeVorkin L, Macpherson S, Jirasek A, Lum JJ, Brolo AG. Ex vivo detection of circulating tumor cells from whole blood by direct nanoparticle visualization. ACS Nano. 2018;12:1902–9.CrossRefGoogle Scholar
  54. 54.
    Rothe F, Silva MJ, Venet D, Campbell C, Bradburry I, Rouas G et al. Circulating tumor DNA in HER2-amplified breast cancer: a translational research substudy of the NeoALTTO phase III trial. Clin Cancer Res. 2019.Google Scholar
  55. 55.
    Ignatiadis M, Litiere S, Rothe F, Riethdorf S, Proudhon C, Fehm T, et al. Trastuzumab versus observation for HER2 nonamplified early breast cancer with circulating tumor cells (EORTC 90091-10093, BIG 1-12, Treat CTC): a randomized phase II trial. Ann Oncol. 2018;29:1777–83.CrossRefGoogle Scholar
  56. 56.
    Jaeger BAS, Neugebauer J, Andergassen U, Melcher C, Schochter F, Mouarrawy D, et al. The HER2 phenotype of circulating tumor cells in HER2-positive early breast cancer: a translational research project of a prospective randomized phase III trial. PLoS ONE. 2017;12:e0173593.CrossRefGoogle Scholar
  57. 57.
    Schramm A, Schochter F, Friedl TWP, de Gregorio N, Andergassen U, Alunni-Fabbroni M, et al. Prevalence of circulating tumor cells after adjuvant chemotherapy with or without anthracyclines in patients with HER2-negative, hormone receptor-positive early breast cancer. Clin Breast Cancer. 2017;17:279–85.CrossRefGoogle Scholar
  58. 58.
    Wallwiener M, Hartkopf AD, Riethdorf S, Nees J, Sprick MR, Schonfisch B, et al. The impact of HER2 phenotype of circulating tumor cells in metastatic breast cancer: a retrospective study in 107 patients. BMC Cancer. 2015;15:403.CrossRefGoogle Scholar
  59. 59.
    Jakabova A, Bielcikova Z, Pospisilova E, Matkowski R, Szynglarewicz B, Staszek-Szewczyk U, et al. Molecular characterization and heterogeneity of circulating tumor cells in breast cancer. Breast Cancer Res Treat. 2017;166:695–700.CrossRefGoogle Scholar
  60. 60.
    Jahr S, Hentze H, Englisch S, Hardt D, Fackelmayer FO, Hesch RD, et al. DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Can Res. 2001;61:1659–65.Google Scholar
  61. 61.
    Canzoniero JV, Park BH. Use of cell free DNA in breast oncology. Biochem Biophys Acta. 2016;1865:266–74.Google Scholar
  62. 62.
    Elshimali YI, Khaddour H, Sarkissyan M, Wu Y, Vadgama JV. The clinical utilization of circulating cell free DNA (CCFDNA) in blood of cancer patients. Int J Mol Sci. 2013;14:18925–58.CrossRefGoogle Scholar
  63. 63.
    Kirsch C, Weickmann S, Schmidt B, Fleischhacker M. An improved method for the isolation of free-circulating plasma DNA and cell-free DNA from other body fluids. Ann N Y Acad Sci. 2008;1137:135–9.CrossRefGoogle Scholar
  64. 64.
    Atamaniuk J, Vidotto C, Tschan H, Bachl N, Stuhlmeier KM, Muller MM. Increased concentrations of cell-free plasma DNA after exhaustive exercise. Clin Chem. 2004;50:1668–70.CrossRefGoogle Scholar
  65. 65.
    Breitbach S, Tug S, Simon P. Circulating cell-free DNA: an up-coming molecular marker in exercise physiology. Sports Med (Auckland, NZ). 2012;42:565–86.CrossRefGoogle Scholar
  66. 66.
    Esposito A, Criscitiello C, Locatelli M, Milano M, Curigliano G. Liquid biopsies for solid tumors: understanding tumor heterogeneity and real time monitoring of early resistance to targeted therapies. Pharmacol Ther. 2016;157:120–4.CrossRefGoogle Scholar
  67. 67.
    Thompson JC, Yee SS, Troxel AB, Savitch SL, Fan R, Balli D, et al. Detection of therapeutically targetable driver and resistance mutations in lung cancer patients by next-generation sequencing of cell-free circulating tumor DNA. Clin Cancer Res. 2016;22:5772–82.CrossRefGoogle Scholar
  68. 68.
    Korfhage C, Fricke E, Meier A. Parallel WGA and WTA for comparative genome and transcriptome NGS analysis using tiny cell numbers. Curr Protoc Mol Biol. 2015;111:7.19.1-8.Google Scholar
  69. 69.
    Iqbal S, Vishnubhatla S, Raina V, Sharma S, Gogia A, Deo SS, et al. Circulating cell-free DNA and its integrity as a prognostic marker for breast cancer. Springer Plus. 2015;4:265.CrossRefGoogle Scholar
  70. 70.
    Sozzi G, Conte D, Leon M, Ciricione R, Roz L, Ratcliffe C, et al. Quantification of free circulating DNA as a diagnostic marker in lung cancer. J Clin Oncol. 2003;21:3902–8.CrossRefGoogle Scholar
  71. 71.
    Tie J, Wang Y, Tomasetti C, Li L, Springer S, Kinde I, et al. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med. 2016;8:346ra92.CrossRefGoogle Scholar
  72. 72.
    Lou QGJ. Research progresses of circulating tumor DNA. Chin J Cancer Biother 2016.Google Scholar
  73. 73.
    De Luca F, Rotunno G, Salvianti F, Galardi F, Pestrin M, Gabellini S, et al. Mutational analysis of single circulating tumor cells by next generation sequencing in metastatic breast cancer. Oncotarget. 2016;18:26107–19.Google Scholar
  74. 74.
    Bulfoni M, Gerratana L, Del Ben F, Marzinotto S, Sorrentino M, Turetta M, et al. In patients with metastatic breast cancer the identification of circulating tumor cells in epithelial-to-mesenchymal transition is associated with a poor prognosis. Breast Cancer Res. 2016;18:30.CrossRefGoogle Scholar
  75. 75.
    Cristofanilli M, Hayes DF, Budd GT, Ellis MJ, Stopeck A, Reuben JM, et al. Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin Oncol. 2005;23:1420–30.CrossRefGoogle Scholar
  76. 76.
    Lang JE, Ring A, Porras T, Kaur P, Forte VA, Mineyev N, et al. RNA-Seq of circulating tumor cells in stage II-III breast cancer. Ann Surg Oncol. 2018;25:2261–70.CrossRefGoogle Scholar
  77. 77.
    Thress KS, Brant R, Carr TH, Dearden S, Jenkins S, Brown H, et al. EGFR mutation detection in ctDNA from NSCLC patient plasma: a cross-platform comparison of leading technologies to support the clinical development of AZD9291. Lung Cancer (Amsterdam, Netherlands). 2015;90:509–15.CrossRefGoogle Scholar
  78. 78.
    Halvaei S, Daryani S, Eslami SZ, Samadi T, Jafarbeik-Iravani N, Bakhshayesh TO, et al. Exosomes in cancer liquid biopsy: a focus on breast cancer. Mol Ther Nucleic Acids. 2018;10:131–41.CrossRefGoogle Scholar
  79. 79.
    Akagi T, Kato K, Kobayashi M, Kosaka N, Ochiya T, Ichiki T. On-chip immunoelectrophoresis of extracellular vesicles released from human breast cancer cells. PLoS ONE. 2015;10:e0123603.CrossRefGoogle Scholar
  80. 80.
    Chahar HS, Bao X, Casola A. Exosomes and their role in the life cycle and pathogenesis of RNA viruses. Viruses. 2015;7:3204–25.CrossRefGoogle Scholar
  81. 81.
    Wang X, Zhong W, Bu J, Li Y, Li R, Nie R, et al. Exosomal protein CD82 as a diagnostic biomarker for precision medicine for breast cancer. Mol Carcinog. 2019;58:674–85.CrossRefGoogle Scholar
  82. 82.
    Son D, Kim Y, Lim S, Kang HG, Kim DH, Park JW, et al. miR-374a-5p promotes tumor progression by targeting ARRB1 in triple negative breast cancer. Cancer Lett. 2019;454:224–33.CrossRefGoogle Scholar
  83. 83.
    Alix-Panabieres C, Pantel K. Clinical applications of circulating tumor cells and circulating tumor DNA as liquid biopsy. Cancer Discov. 2016;6:479–91.CrossRefGoogle Scholar
  84. 84.
    Tuomela J, Sandholm J, Kaakinen M, Patel A, Kauppila JH, Ilvesaro J, et al. DNA from dead cancer cells induces TLR9-mediated invasion and inflammation in living cancer cells. Breast Cancer Res Treat. 2013;142:477–87.CrossRefGoogle Scholar
  85. 85.
    Huebner H, Fasching PA, Gumbrecht W, Jud S, Rauh C, Matzas M, et al. Filtration based assessment of CTCs and Cell Search(R) based assessment are both powerful predictors of prognosis for metastatic breast cancer patients. BMC Cancer. 2018;18:204.CrossRefGoogle Scholar
  86. 86.
    Bidard FC, Peeters DJ, Fehm T, Nole F, Gisbert-Criado R, Mavroudis D, et al. Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data. Lancet Oncol. 2014;15:406–14.CrossRefGoogle Scholar
  87. 87.
    Bidard FC, Michiels S, Riethdorf S, Mueller V, Esserman LJ, Lucci A, et al. Circulating tumor cells in breast cancer patients treated by neoadjuvant chemotherapy: a meta-analysis. J Natl Cancer Inst. 2018;110:560–7.CrossRefGoogle Scholar
  88. 88.
    American Joint Committee on Cancer (2018) Updated breast chapter for 8th edition. Accessed 25 January 2018. https://cancerstaging.org/references-tools/deskreferences/Pages/Breast-Cancer-Staging.aspx.
  89. 89.
    Dawson SJ, Rosenfeld N, Caldas C. Circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med. 2013;369:93–4.CrossRefGoogle Scholar
  90. 90.
    Rossi G, Mu Z, Rademaker AW, Austin LK, Strickland KS, Costa RLB, et al. Cell-free DNA and circulating tumor cells: comprehensive liquid biopsy analysis in advanced breast cancer. Clin Cancer Res. 2018;24:560–8.CrossRefGoogle Scholar
  91. 91.
    Babayan A, Pantel K. Advances in liquid biopsy approaches for early detection and monitoring of cancer. Genome Med. 2018;10:21.CrossRefGoogle Scholar
  92. 92.
    Paoletti C, Cani AK, Larios JM, Hovelson DH, Aung K, Darga EP, et al. Comprehensive mutation and copy number profiling in archived circulating breast cancer tumor cells documents heterogeneous resistance mechanisms. Can Res. 2018;78:1110–22.CrossRefGoogle Scholar
  93. 93.
    Aktas B, Muller V, Tewes M, Zeitz J, Kasimir-Bauer S, Loehberg CR, et al. Comparison of estrogen and progesterone receptor status of circulating tumor cells and the primary tumor in metastatic breast cancer patients. Gynecol Oncol. 2011;122:356–60.CrossRefGoogle Scholar
  94. 94.
    Garcia-Murillas I, Schiavon G, Weigelt B, Ng C, Hrebien S, Cutts RJ, et al. Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. Sci Transl Med. 2015;7:302ra133.CrossRefGoogle Scholar
  95. 95.
    Sundaresan TK, Haber DA. Does molecular monitoring matter in early-stage breast cancer? Sci Transl Med. 2015;7:302fs35.CrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Laboratory MedicineAffiliated Hospital of Nantong UniversityNantongChina

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