Skip to main content

Advertisement

SpringerLink
Log in

Prognostic and Predictive Role of Circulating Tumor Cells in Breast Cancer

  • Biomarkers (S Dawood, Section Editor)
  • Published:
Current Breast Cancer Reports Aims and scope Submit manuscript

Abstract

Circulating tumor cells (CTCs) play a crucial role in metastatic cascade, tumor dissemination, and progression. CTCs represent a unique biomarker, as they are cancer cells and sampling of a patient's tumor. CTCs are a heterogeneous cell population of tumor cells with different phenotypes and biological values, with established prognostic impact in primary and metastatic breast cancer. Detection and molecular profiling of CTCs could represent a valuable prognostic and predictive factor, a tool for tumor ‘liquid’ biopsy in real time and for personalized anticancer treatment. Several trials are ongoing aimed to demonstrate clinical utility of CTCs detection and profiling to facilitate rational treatment decisions for breast cancer patients. Therapeutic targeting of CTCs might be a promising strategy to interfere with metastatic cascade and tumor dissemination.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9–29.

    Article  PubMed  Google Scholar 

  2. Greenberg PA, Hortobagyi GN, Smith TL, Ziegler LD, Frye DK, Buzdar AU. Long-term follow-up of patients with complete remission following combination chemotherapy for metastatic breast cancer. J Clin Oncol. 1996;14:2197–205.

    CAS  PubMed  Google Scholar 

  3. Fidler IJ. The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer. 2003;3:453–8.

    Article  CAS  PubMed  Google Scholar 

  4. Butler TP, Gullino PM. Quantitation of cell shedding into efferent blood of mammary adenocarcinoma. Cancer Res. 1975;35:512–6.

    CAS  PubMed  Google Scholar 

  5. Wong CW, Lee A, Shientag L, Yu J, Dong Y, Kao G, et al. Apoptosis: an early event in metastatic inefficiency. Cancer Res. 2001;61:333–8.

    CAS  PubMed  Google Scholar 

  6. Baccelli I, Schneeweiss A, Riethdorf S, Stenzinger A, Schillert A, Vogel V, et al. Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay. Nat Biotechnol. 2013;31:539–44. Seminal paper that, for the first time, experimentally demonstrated the existence and phenotype of metastasis-initiating cells (MICs) among CTCs.

    Article  CAS  PubMed  Google Scholar 

  7. Kim MY, Oskarsson T, Acharyya S, Nguyen DX, Zhang XH, Norton L, et al. Tumor self-seeding by circulating cancer cells. Cell. 2009;139:1315–26.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Comen E, Norton L, Massagué J. Clinical implications of cancer self-seeding. Nat Rev Clin Oncol. 2011;8:369–77.

    PubMed  Google Scholar 

  9. Scheel C, Weinberg RA. Cancer stem cells and epithelial-mesenchymal transition: concepts and molecular links. Semin Cancer Biol. 2012;22:396–403.

    Article  CAS  PubMed  Google Scholar 

  10. Yu M, Bardia A, Wittner BS, Stott SL, Smas ME, Ting DT, et al. Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science. 2013;339:580–4. In this paper authors showed the continuum of CTCs from epithelial to mesenchymal phenotype and the role of EMT in the blood-borne dissemination of human breast cancer.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Mego M, Mani SA, Lee BN, Li C, Evans KW, Cohen EN, et al. Expression of epithelial-mesenchymal transition-inducing transcription factors in primary breast cancer: the effect of neoadjuvant therapy. Int J Cancer. 2012;130:808–16.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Gorges TM, Tinhofer I, Drosch M, Röse L, Zollner TM, Krahn T, et al. Circulating tumour cells escape from EpCAM-based detection due to epithelial-to-mesenchymal transition. BMC Cancer. 2012;12:178.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Königsberg R, Obermayr E, Bises G, Pfeiler G, Gneist M, Wrba F, et al. Detection of EpCAM positive and negative circulating tumor cells in metastatic breast cancer patients. Acta Oncol. 2011;50:700–10.

    Article  PubMed  Google Scholar 

  14. Moustakas A, Heldin CH. Signaling networks guiding epithelial-mesenchymal transitions during embryogenesis and cancer progression. Cancer Sci. 2007;98:1512–20.

    Article  CAS  PubMed  Google Scholar 

  15. Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, et al. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell. 2004;117:927–39.

    Article  CAS  PubMed  Google Scholar 

  16. Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133:704–15.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Grover PK, Cummins AG, Price TJ, Roberts-Thomson IC, Hardingham JE. Circulating tumour cells: the evolving concept and the inadequacy of their enrichment by EpCAM-based methodology for basic and clinical cancer research. Ann Oncol. 2014. [Epub ahead of print]. PubMed PMID: 24651410.

  18. Biddle A, Liang X, Gammon L, Fazil B, Harper LJ, Emich H, et al. Cancer stem cells in squamous cell carcinoma switch between two distinct phenotypes that are preferentially migratory or proliferative. Cancer Res. 2011;71:5317–26.

    Article  CAS  PubMed  Google Scholar 

  19. Mego M, Gao H, Lee BN, Cohen EN, Tin S, Giordano A, et al. Prognostic value of EMT-circulating tumor cells in metastatic breast cancer patients undergoing high-dose chemotherapy with autologous hematopoietic stem cell transplantation. J Cancer. 2012;3:369–80.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Giordano A, Gao H, Anfossi S, Cohen E, Mego M, Lee BN, et al. Epithelial-mesenchymal transition and stem cell markers in patients with HER2-positive metastatic breast cancer. Mol Cancer Ther. 2012;11:2526–34.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Bast Jr RC, Ravdin P, Hayes DF, Bates S, Fritsche Jr H, Jessup JM, et al. American Society of Clinical Oncology Tumor Markers Expert Panel. 2000 update of recommendations for the use of tumor markers in breast and colorectal cancer: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol. 2001;19:1865–78.

    PubMed  Google Scholar 

  22. Hortobagyi GN, Smith TL, Legha SS, Swenerton KD, Gehan EA, Yap HY, et al. Multivariate analysis of prognostic factors in metastatic breast cancer. J Clin Oncol. 1983;1:776–86.

    CAS  PubMed  Google Scholar 

  23. Hayes DF. Prognostic and predictive factors revisited. Breast. 2005;14:493–9.

    Article  PubMed  Google Scholar 

  24. Ashworth TR. A case of cancer in which cells similar to those in the tumours were seen in the blood after death. Aust Med J. 1869;14:146–9.

    Google Scholar 

  25. 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.

    Article  CAS  PubMed  Google Scholar 

  26. Alix-Panabières C, Brouillet JP, Fabbro M, Yssel H, Rousset T, Maudelonde T, et al. Characterization and enumeration of cells secreting tumor markers in the peripheral blood of breast cancer patients. J Immunol Methods. 2005;299:177–88.

    Article  PubMed  Google Scholar 

  27. Warkiani ME, Guan G, Luan KB, Lee WC, Bhagat AA, Chaudhuri PK, et al. Slanted spiral microfluidics for the ultra-fast, label-free isolation of circulating tumor cells. Lab Chip. 2014;14:128–37.

    Article  CAS  PubMed  Google Scholar 

  28. Zheng S, Lin HK, Lu B, Williams A, Datar R, Cote RJ, et al. 3D microfilter device for viable circulating tumor cell (CTC) enrichment from blood. Biomed Microdevices. 2011;13:203–13.

    Article  PubMed  Google Scholar 

  29. Pachmann K, Camara O, Kavallaris A, Krauspe S, Malarski N, Gajda M, et al. Monitoring the response of circulating epithelial tumor cells to adjuvant chemotherapy in breast cancer allows detection of patients at risk of early relapse. J Clin Oncol. 2008;26:1208–15.

    Article  PubMed  Google Scholar 

  30. Nagrath S, Sequist LV, Maheswaran S, Bell DW, Irimia D, Ulkus L, et al. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature. 2007;450:1235–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Hsieh HB, Marrinucci D, Bethel K, Curry DN, Humphrey M, Krivacic RT, et al. High speed detection of circulating tumor cells. Biosens Bioelectron. 2006;21:1893–9.

    Article  CAS  PubMed  Google Scholar 

  32. Talasaz AH, Powell AA, Huber DE, Berbee JG, Roh KH, Yu W, et al. Isolating highly enriched populations of circulating epithelial cells and other rare cells from blood using a magnetic sweeper device. Proc Natl Acad Sci U S A. 2009;106:3970–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Saucedo-Zeni N, Mewes S, Niestroj R, Gasiorowski L, Murawa D, Nowaczyk P, et al. A novel method for the in vivo isolation of circulating tumor cells from peripheral blood of cancer patients using a functionalized and structured medical wire. Int J Oncol. 2012;41:1241–50.

    PubMed Central  PubMed  Google Scholar 

  34. Mego M, Mani SA, Cristofanilli M. Molecular mechanisms of metastasis in breast cancer—clinical applications. Nat Rev Clin Oncol. 2010;7:693–701.

    Article  CAS  PubMed  Google Scholar 

  35. Lucci A, Hall CS, Lodhi AK, Bhattacharyya A, Anderson AE, Xiao L, et al. Circulating tumour cells in non-metastatic breast cancer: a prospective study. Lancet Oncol. 2012;13:688–95. First study that showed prognostic role of CTCs detected by CellSearch in primary breast cancer. In this study CTCs were detected in 7.5 mL of peripheral blood.

    Article  PubMed  Google Scholar 

  36. Zhang L, Riethdorf S, Wu G, Wang T, Yang K, Peng G, et al. Meta-analysis of the prognostic value of circulating tumor cells in breast cancer. Clin Cancer Res. 2012;18:5701–10. Comprehensive meta-analysis of CTCs detected with various detection methods in primary and metastatic breast cancer.

    Article  PubMed  Google Scholar 

  37. Zhao S, Liu Y, Zhang Q, Li H, Zhang M, Ma W, et al. The prognostic role of circulating tumor cells (CTCs) detected by RT-PCR in breast cancer: a meta-analysis of published literature. Breast Cancer Res Treat. 2011;130:809–16. Comprehensive meta-analysis of CTCs detected with RT-PCR in breast cancer.

    Article  PubMed  Google Scholar 

  38. Bidard FC, Peeters DJ, Fehm T, Nolé 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. First pooled analysis of trials that evaluated prognostic value of CTC detected by CellSearch in metastatic breast cancer.

    Article  PubMed  Google Scholar 

  39. 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.

    Article  PubMed  Google Scholar 

  40. Budd GT, Cristofanilli M, Ellis MJ, Stopeck A, Borden E, Miller MC, et al. Circulating tumor cells vs imaging—predicting overall survival in metastatic breast cancer. Clin Cancer Res. 2006;12:6403–9.

    Article  CAS  PubMed  Google Scholar 

  41. De Giorgi U, Valero V, Rohren E, Dawood S, Ueno NT, Miller MC, et al. Circulating tumor cells and [18F]fluorodeoxyglucose positron emission tomography/computed tomography for outcome prediction in metastatic breast cancer. J Clin Oncol. 2009;27:3303–11.

    Article  PubMed  Google Scholar 

  42. Dawood S, Broglio K, Valero V, Reuben J, Handy B, Islam R, et al. Circulating tumor cells in metastatic breast cancer: from prognostic stratification to modification of the staging system? Cancer. 2008;113:2422–30.

    Article  PubMed  Google Scholar 

  43. Giuliano M, Giordano A, Jackson S, Hess KR, De Giorgi U, Mego M, et al. Circulating tumor cells as prognostic and predictive markers in metastatic breast cancer patients receiving first-line systemic treatment. Breast Cancer Res. 2011;13:R67. Important large study, that demonstrated prognostic and predictive role of CTCs in MBC patients based on single institution experience.

    Article  PubMed Central  PubMed  Google Scholar 

  44. Nakamura S, Yagata H, Ohno S, Yamaguchi H, Iwata H, Tsunoda N, et al. Multi-center study evaluating circulating tumor cells as a surrogate for response to treatment and overall survival in metastatic breast cancer. Breast Cancer. 2010;17:199–204.

    Article  PubMed  Google Scholar 

  45. Nolé F, Munzone E, Zorzino L, Minchella I, Salvatici M, Botteri E, et al. Variation of circulating tumor cell levels during treatment of metastatic breast cancer: prognostic and therapeutic implications. Ann Oncol. 2008;19:891–7.

    Article  PubMed  Google Scholar 

  46. Liu MC, Shields PG, Warren RD, Cohen P, Wilkinson M, Ottaviano YL, et al. Circulating tumor cells: a useful predictor of treatment efficacy in metastatic breast cancer. J Clin Oncol. 2009;27:5153–9.

    Article  PubMed  Google Scholar 

  47. Pierga JY, Hajage D, Bachelot T, Delaloge S, Brain E, Campone M, et al. High independent prognostic and predictive value of circulating tumor cells compared with serum tumor markers in a large prospective trial in first-line chemotherapy for metastatic breast cancer patients. Ann Oncol. 2012;23:618–24.

    Article  PubMed  Google Scholar 

  48. Giordano A, Giuliano M, De Laurentiis M, Arpino G, Jackson S, Handy BC, et al. Circulating tumor cells in immunohistochemical subtypes of metastatic breast cancer: lack of prediction in HER2-positive disease treated with targeted therapy. Ann Oncol. 2012;23:1144–50.

    Article  CAS  PubMed  Google Scholar 

  49. Liu MC, Mego M, Nakamura S, Nole F, Pierga J, Toi M, et al. Clinical validity of circulating tumor cell (CTC) enumeration in 841 subjects with metastatic breast cancer (MBC). J Clin Oncol. 2011;29:(Suppl): [Abstract 10592].

  50. Bidard FC, Mathiot C, Degeorges A, Etienne-Grimaldi MC, Delva R, Pivot X, et al. Clinical value of circulating endothelial cells and circulating tumor cells in metastatic breast cancer patients treated first line with bevacizumab and chemotherapy. Ann Oncol. 2010;21:1765–71.

    Article  PubMed  Google Scholar 

  51. Mego M, De Giorgi U, Limin H, Dawood S, Andreopoulou E, Valero V, et al. Predictive value of circulating tumor cells (CTCs) in metastatic breast cancer patients treated by bevacizumab-based therapy. Cancer Res. 2009;69 Suppl 24:573. s: [Abstract 3013].

    Google Scholar 

  52. Wallwiener M, Hartkopf AD, Baccelli I, Riethdorf S, Schott S, Pantel K, et al. The prognostic impact of circulating tumor cells in subtypes of metastatic breast cancer. Breast Cancer Res Treat. 2013;137:503–10.

    Article  PubMed  Google Scholar 

  53. Rack B, Schindlbeck C, Jückstock J, Andergassen U, Hepp P, Zwingers T, et al. Circulating tumor cells predict survival in early average-to-high risk breast cancer patients. J Natl Cancer Inst. 2014;106(5). pii: dju066. doi: 10.1093/jnci/dju066. PubMed PMID: 24832787. Largest study that showed prognostic role of CTCs detected by the CellSearch in primary breast cancer. In this study CTCs were detected in 23 mL of peripheral blood.

  54. Bidard FC, Belin L, Delaloge S, Lerebours F, Ngo C, Reyal F, et al. Time-dependent prognostic impact of circulating tumor cells detection in non-metastatic breast cancer: 70-month analysis of the REMAGUS02 Study. Int J Breast Cancer. 2013;2013:130470.

    Article  PubMed Central  PubMed  Google Scholar 

  55. Janni WJ, Rack BK, Terstappen LMWW, Pierga J-Y, Fehm T, Hall C, et al. A pooled analysis of the prognostic relevance of circulating tumor cells in early breast cancer. Cancer Res. 2013;73(24 Suppl): [Abstract nr PD6-6]. First pooled analysis of trials that evaluated prognostic value of CTC detected by CellSearch in primary breast cancer.

  56. Smerage JB, Barlow WE, Hortobagyi GN, Winer EP, Leyland-Jones B, Srkalovic G, et al. Circulating tumor cells and response to chemotherapy in metastatic breast cancer: SWOG S0500. J Clin Oncol. 2014; [Epub ahead of print]. pii: JCO.2014.56.2561. PubMed PMID: 24888818. Seminal study, that failed to showed clinical utility of CTCs in treatment decision making in MBC, but confirmed prognostic value of CTCs. This trial found that changing therapy for patients with elevated CTCs after 1 cycle of initial chemotherapy did not improve their overall survival.

  57. Flores LM, Kindelberger DW, Ligon AH, Capelletti M, Fiorentino M, Loda M, et al. Improving the yield of circulating tumour cells facilitates molecular characterisation and recognition of discordant HER2 amplification in breast cancer. Br J Cancer. 2010;102:1495–502.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  58. Reuben JM, Lee BN, Li C, Gao H, Broglio KR, Valero V, et al. Circulating tumor cells and biomarkers: implications for personalized targeted treatments for metastatic breast cancer. Breast J. 2010;16:327–30.

    Article  PubMed  Google Scholar 

  59. Fehm T, Hoffmann O, Aktas B, Becker S, Solomayer EF, Wallwiener D, et al. Detection and characterization of circulating tumor cells in blood of primary breast cancer patients by RT-PCR and comparison to status of bone marrow disseminated cells. Breast Cancer Res. 2009;11:R59.

    Article  PubMed Central  PubMed  Google Scholar 

  60. Hayashi N, Nakamura S, Tokuda Y, Shimoda Y, Yagata H, Yoshida A, et al. Prognostic value of HER2-positive circulating tumor cells in patients with metastatic breast cancer. Int J Clin Oncol. 2012;17:96–104.

    Article  PubMed  Google Scholar 

  61. Riethdorf S, Müller V, Zhang L, Rau T, Loibl S, Komor M, et al. Detection and HER2 expression of circulating tumor cells: prospective monitoring in breast cancer patients treated in the neoadjuvant GeparQuattro trial. Clin Cancer Res. 2010;16:2634–45.

    Article  CAS  PubMed  Google Scholar 

  62. Munzone E, Nolé F, Goldhirsch A, Botteri E, Esposito A, Zorzino L, et al. Changes of HER2 status in circulating tumor cells compared with the primary tumor during treatment for advanced breast cancer. Clin Breast Cancer. 2010;10:392–7.

    Article  CAS  PubMed  Google Scholar 

  63. Ligthart ST, Bidard FC, Decraene C, Bachelot T, Delaloge S, Brain E, et al. Unbiased quantitative assessment of Her-2 expression of circulating tumor cells in patients with metastatic and non-metastatic breast cancer. Ann Oncol. 2013;24:1231–8.

    Article  CAS  PubMed  Google Scholar 

  64. Meng S, Tripathy D, Shete S, Ashfaq R, Haley B, Perkins S, et al. HER-2 gene amplification can be acquired as breast cancer progresses. Proc Natl Acad Sci U S A. 2004;101:9393–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  65. Liu Y, Liu Q, Wang T, Bian L, Zhang S, Hu H, et al. Circulating tumor cells in HER2-positive metastatic breast cancer patients: a valuable prognostic and predictive biomarker. BMC Cancer. 2013;13:202.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  66. Pestrin M, Bessi S, Puglisi F, Minisini AM, Masci G, Battelli N, et al. Final results of a multicenter phase II clinical trial evaluating the activity of single-agent lapatinib in patients with HER2-negative metastatic breast cancer and HER2-positive circulating tumor cells. A proof-of-concept study. Breast Cancer Res Treat. 2012;134:283–9.

    Article  CAS  PubMed  Google Scholar 

  67. Stebbing J, Payne R, Reise J, Frampton AE, Avery M, Woodley L, et al. The efficacy of lapatinib in metastatic breast cancer with HER2 non-amplified primary tumors and EGFR positive circulating tumor cells: a proof-of-concept study. PLoS One. 2013;8:e62543.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  68. Bonneterre J, Thürlimann B, Robertson JF, Krzakowski M, Mauriac L, Koralewski P, et al. Anastrozole vs tamoxifen as first-line therapy for advanced breast cancer in 668 postmenopausal women: results of the Tamoxifen or Arimidex Randomized Group Efficacy and Tolerability study. J Clin Oncol. 2000;18:3748–57.

    CAS  PubMed  Google Scholar 

  69. Mouridsen H, Gershanovich M, Sun Y, Perez-Carrion R, Boni C, Monnier A, et al. Phase III study of letrozole vs tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: analysis of survival and update of efficacy from the International Letrozole Breast Cancer Group. J Clin Oncol. 2003;21:2101–9.

    Article  CAS  PubMed  Google Scholar 

  70. Babayan A, Hannemann J, Spötter J, Müller V, Pantel K, Joosse SA. Heterogeneity of estrogen receptor expression in circulating tumor cells from metastatic breast cancer patients. PLoS One. 2013;8:e75038.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  71. Aktas B, Müller 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.

    Article  CAS  PubMed  Google Scholar 

  72. Smerage JB, Budd GT, Doyle GV, Brown M, Paoletti C, Muniz M, et al. Monitoring apoptosis and Bcl-2 on circulating tumor cells in patients with metastatic breast cancer. Mol Oncol. 2013;7:680–92.

    Article  CAS  PubMed  Google Scholar 

  73. Gazzaniga P, Naso G, Gradilone A, Cortesi E, Gandini O, Gianni W, et al. Chemosensitivity profile assay of circulating cancer cells: prognostic and predictive value in epithelial tumors. Int J Cancer. 2010;126:2437–47.

    CAS  PubMed  Google Scholar 

  74. Schneck H, Blassl C, Meier-Stiegen F, Neves RP, Janni W, Fehm T, et al. Analysing the mutational status of PIK3CA in circulating tumor cells from metastatic breast cancer patients. Mol Oncol. 2013;7:976–86.

    Article  CAS  PubMed  Google Scholar 

  75. Pizon M, Zimon DS, Pachmann U, Pachmann K. Insulin-like growth factor receptor I (IGF-IR) and vascular endothelial growth factor receptor 2 (VEGFR-2) are expressed on the circulating epithelial tumor cells of breast cancer patients. PLoS One. 2013;8:e56836.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  76. Rossi E, Basso U, Celadin R, Zilio F, Pucciarelli S, Aieta M, et al. M30 neoepitope expression in epithelial cancer: quantification of apoptosis in circulating tumor cells by Cell Search analysis. Clin Cancer Res. 2010;16:5233–43.

    Article  CAS  PubMed  Google Scholar 

  77. Heitzer E, Auer M, Gasch C, Pichler M, Ulz P, Hoffmann EM, et al. Cancer Res. 2013;73:2965–75. This study demonstrated feasibility of NGS to detect mutation in CTCs.

    Article  CAS  PubMed  Google Scholar 

  78. Turner N, Pestrin M, Galardi F, De Luca F, Malorni L, Di Leo A. Can biomarker assessment on circulating tumor cells help direct therapy in metastatic breast cancer? Cancers (Basel). 2014;6:684–707. Comprehensive review article related to biomarker assessment of CTCs.

    Article  CAS  Google Scholar 

  79. Turner NH, Di Leo A. HER2 discordance between primary and metastatic breast cancer: assessing the clinical impact. Cancer Treat Rev. 2013;39:947–57.

    Article  CAS  PubMed  Google Scholar 

  80. Pusztai L, Viale G, Kelly CM, Hudis CA. Estrogen and HER-2 receptor discordance between primary breast cancer and metastasis. Oncologist. 2010;15:1164–8.

    Article  PubMed Central  PubMed  Google Scholar 

  81. Mego M, De Giorgi U, Dawood S, Wang X, Valero V, Andreopoulou E, et al. Characterization of metastatic breast cancer patients with nondetectable circulating tumor cells. Int J Cancer. 2011;129:417–23.

    Article  CAS  PubMed  Google Scholar 

  82. Friedlander TW, Fong L. The end of the beginning: circulating tumor cells as a biomarker in castration-resistant prostate cancer. J Clin Oncol. 2014;32:1104–6.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgement

This publication is the result of the implementation of project funded by the Slovak Grant Agency VEGA 1/0724/11.

Compliance with Ethics Guidelines

ᅟ

Conflict of Interest

Michal Mego and James M Reuben declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with animal subjects performed by any of the authors. With regard to the authors’ research cited in this paper, all procedures were followed in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2000 and 2008.

Author information

Authors and Affiliations

  1. 2nd Department of Medical Oncology, Faculty of Medicine, National Cancer Institute, Comenius University, Klenova 1, 833 10, Bratislava, Slovak Republic

    Michal Mego

  2. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA

    James M. Reuben

Authors
  1. Michal Mego
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. James M. Reuben
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michal Mego.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mego, M., Reuben, J.M. Prognostic and Predictive Role of Circulating Tumor Cells in Breast Cancer. Curr Breast Cancer Rep 6, 251–259 (2014). https://doi.org/10.1007/s12609-014-0164-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12609-014-0164-x

Keywords

Search

Navigation