International Journal of Clinical Oncology

, Volume 22, Issue 3, pp 421–430 | Cite as

Circulating tumor cells: clinical validity and utility

  • Luc Cabel
  • Charlotte Proudhon
  • Hugo Gortais
  • Delphine Loirat
  • Florence Coussy
  • Jean-Yves Pierga
  • François-Clément Bidard
Invited Review Article

Abstract

Circulating tumor cells (CTCs) are rare tumor cells and have been investigated as diagnostic, prognostic and predictive biomarkers in many types of cancer. Although CTCs are not currently used in clinical practice, CTC studies have accumulated a high level of clinical validity, especially in breast, lung, prostate and colorectal cancers. In this review, we present an overview of the current clinical validity of CTCs in metastatic and non-metastatic disease, and the main concepts and studies investigating the clinical utility of CTCs. In particular, this review will focus on breast, lung, colorectal and prostate cancer. Three major topics concerning the clinical utility of CTC are discussed—(1) treatment based on CTCs used as liquid biopsy, (2) treatment based on CTC count or CTC variations, and (3) treatment based on CTC biomarker expression. A summary of published or ongoing phase II and III trials is also presented.

Keywords

Circulating tumor cells Clinical validity Clinical utility Biomarkers Clinical trials 

References

  1. 1.
    Ashworth TR (1869) 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: 146−147Google Scholar
  2. 2.
    Ferreira MM, Ramani VC, Jeffrey SS (2016) Circulating tumor cell technologies. Mol Oncol 10:374–394. doi:10.1016/j.molonc.2016.01.007 CrossRefPubMedGoogle Scholar
  3. 3.
    Coumans FAW, Ligthart ST, Uhr JW et al (2012) Challenges in the enumeration and phenotyping of CTC. Clin Cancer Res Off J Am Assoc Cancer Res 18:5711–5718. doi:10.1158/1078-0432.CCR-12-1585 CrossRefGoogle Scholar
  4. 4.
    Kirby BJ, Jodari M, Loftus MS et al (2012) Functional characterization of circulating tumor cells with a prostate-cancer-specific microfluidic device. PLoS One 7:e35976. doi:10.1371/journal.pone.0035976 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Raimondi C, Nicolazzo C, Gradilone A et al (2014) Circulating tumor cells: exploring intratumor heterogeneity of colorectal cancer. Cancer Biol Ther 15:496–503. doi:10.4161/cbt.28020 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Harb W, Fan A, Tran T et al (2013) Mutational analysis of circulating tumor cells using a novel microfluidic collection device and qPCR Assay. Transl Oncol 6:528–538CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Pestrin M, Salvianti F, Galardi F et al (2015) Heterogeneity of PIK3CA mutational status at the single cell level in circulating tumor cells from metastatic breast cancer patients. Mol Oncol 9:749–757. doi:10.1016/j.molonc.2014.12.001 CrossRefPubMedGoogle Scholar
  8. 8.
    Mayer JA, Pham T, Wong KL et al (2011) FISH-based determination of HER2 status in circulating tumor cells isolated with the microfluidic CEE™ platform. Cancer Genet 204:589–595. doi:10.1016/j.cancergen.2011.10.011 CrossRefPubMedGoogle Scholar
  9. 9.
    Kanwar N, Hu P, Bedard P et al (2015) Identification of genomic signatures in circulating tumor cells from breast cancer. Int J Cancer 137:332–344. doi:10.1002/ijc.29399 CrossRefPubMedGoogle Scholar
  10. 10.
    Chimonidou M, Kallergi G, Georgoulias V et al (2013) Breast cancer metastasis suppressor-1 promoter methylation in primary breast tumors and corresponding circulating tumor cells. Mol Cancer Res 11:1248–1257. doi:10.1158/1541-7786.MCR-13-0096 CrossRefPubMedGoogle Scholar
  11. 11.
    Mostert B, Sieuwerts AM, Kraan J et al (2015) Gene expression profiles in circulating tumor cells to predict prognosis in metastatic breast cancer patients. Ann Oncol 26:510–516. doi:10.1093/annonc/mdu557 CrossRefPubMedGoogle Scholar
  12. 12.
    Khoo BL, Warkiani ME, Tan DS-W et al (2014) Clinical validation of an ultra high-throughput spiral microfluidics for the detection and enrichment of viable circulating tumor cells. PLoS One 9:e99409. doi:10.1371/journal.pone.0099409 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Ligthart ST, Bidard F-C, Decraene C et al (2013) Unbiased quantitative assessment of Her-2 expression of circulating tumor cells in patients with metastatic and non-metastatic breast cancer. Ann Oncol 24:1231–1238. doi:10.1093/annonc/mds625 CrossRefPubMedGoogle Scholar
  14. 14.
    Gasch C, Oldopp T, Mauermann O et al (2016) Frequent detection of PIK3CA mutations in single circulating tumor cells of patients suffering from HER2-negative metastatic breast cancer. Mol Oncol 10:1330–1343. doi:10.1016/j.molonc.2016.07.005 CrossRefPubMedGoogle Scholar
  15. 15.
    Bidard F-C, Weigelt B, Reis-Filho JS (2013) Going with the flow: from circulating tumor cells to DNA. Sci Transl Med 5:207ps14. doi:10.1126/scitranslmed.3006305 CrossRefPubMedGoogle Scholar
  16. 16.
    Pailler E, Adam J, Barthélémy A et al (2013) Detection of circulating tumor cells harboring a unique ALK rearrangement in ALK-positive non-small-cell lung cancer. J Clin Oncol 31:2273–2281. doi:10.1200/JCO.2012.44.5932 CrossRefPubMedGoogle Scholar
  17. 17.
    Antonarakis ES, Lu C, Wang H et al (2014) AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med 371:1028–1038. doi:10.1056/NEJMoa1315815 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Scher HI, Graf RP, Schreiber NA et al (2016) Nuclear-specific AR-V7 protein localization is necessary to guide treatment selection in metastatic castration-resistant prostate cancer. Eur Urol. doi:10.1016/j.eururo.2016.11.024 Google Scholar
  19. 19.
    Mazel M, Jacot W, Pantel K et al (2015) Frequent expression of PD-L1 on circulating breast cancer cells. Mol Oncol 9:1773–1782. doi:10.1016/j.molonc.2015.05.009 CrossRefPubMedGoogle Scholar
  20. 20.
    Paoletti C, Larios JM, Muñiz MC et al (2016) Heterogeneous estrogen receptor expression in circulating tumor cells suggests diverse mechanisms of fulvestrant resistance. Mol Oncol 10:1078–1085. doi:10.1016/j.molonc.2016.04.006 CrossRefPubMedGoogle Scholar
  21. 21.
    Markowski MC, Frick KD, Eshleman JR et al (2016) Cost-savings analysis of AR-V7 testing in patients with metastatic castration-resistant prostate cancer eligible for treatment with abiraterone or enzalutamide. Prostate 76:1484–1490. doi:10.1002/pros.23232 CrossRefPubMedGoogle Scholar
  22. 22.
    Bidard F-C, Proudhon C, Pierga J-Y (2016) Circulating tumor cells in breast cancer. Mol Oncol 10:418–430. doi:10.1016/j.molonc.2016.01.001 CrossRefPubMedGoogle Scholar
  23. 23.
    Gazzaniga P, Gradilone A, de Berardinis E et al (2012) Prognostic value of circulating tumor cells in nonmuscle invasive bladder cancer: a cell search analysis. Ann Oncol 23:2352–2356. doi:10.1093/annonc/mdr619 CrossRefPubMedGoogle Scholar
  24. 24.
    van Dalum G, Stam G-J, Scholten LFA et al (2015) Importance of circulating tumor cells in newly diagnosed colorectal cancer. Int J Oncol 46:1361–1368. doi:10.3892/ijo.2015.2824 PubMedGoogle Scholar
  25. 25.
    Bork U, Rahbari NN, Schölch S et al (2015) Circulating tumour cells and outcome in non-metastatic colorectal cancer: a prospective study. Br J Cancer 112:1306–1313. doi:10.1038/bjc.2015.88 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Pierga J-Y, Bidard F-C, Mathiot C et al (2008) Circulating tumor cell detection predicts early metastatic relapse after neoadjuvant chemotherapy in large operable and locally advanced breast cancer in a phase II randomized trial. Clin Cancer Res 14:7004–7010. doi:10.1158/1078-0432.CCR-08-0030 CrossRefPubMedGoogle Scholar
  27. 27.
    Magni E, Botteri E, Ravenda PS et al (2014) Detection of circulating tumor cells in patients with locally advanced rectal cancer undergoing neoadjuvant therapy followed by curative surgery. Int J Colorectal Dis 29:1053–1059. doi:10.1007/s00384-014-1958-z CrossRefPubMedGoogle Scholar
  28. 28.
    Loh J, Jovanovic L, Lehman M et al (2014) Circulating tumor cell detection in high-risk non-metastatic prostate cancer. J Cancer Res Clin Oncol 140:2157–2162. doi:10.1007/s00432-014-1775-3 CrossRefPubMedGoogle Scholar
  29. 29.
    Thalgott M, Rack B, Horn T et al (2015) Detection of circulating tumor cells in locally advanced high-risk prostate cancer during neoadjuvant chemotherapy and radical prostatectomy. Anticancer Res 35:5679–5685PubMedGoogle Scholar
  30. 30.
    Bidard FC, Huguet F, Louvet C et al (2013) Circulating tumor cells in locally advanced pancreatic adenocarcinoma: the ancillary CirCe 07 study to the LAP 07 trial. Ann Oncol 24:2057–2061. doi:10.1093/annonc/mdt176 CrossRefPubMedGoogle Scholar
  31. 31.
    Allard WJ, Matera J, Miller MC et al (2004) Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res 10:6897–6904. doi:10.1158/1078-0432.CCR-04-0378 CrossRefPubMedGoogle Scholar
  32. 32.
    Fiorelli A, Accardo M, Carelli E et al (2015) Circulating tumor cells in diagnosing lung cancer: clinical and morphologic analysis. Ann Thorac Surg 99:1899–1905. doi:10.1016/j.athoracsur.2014.11.049 CrossRefPubMedGoogle Scholar
  33. 33.
    Ilie M, Hofman V, Long-Mira E et al (2014) “Sentinel” circulating tumor cells allow early diagnosis of lung cancer in patients with chronic obstructive pulmonary disease. PLoS One 9:e111597. doi:10.1371/journal.pone.0111597 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Bidard F-C, Peeters DJ, Fehm T et al (2014) Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data. Lancet Oncol 15:406–414. doi:10.1016/S1470-2045(14)70069-5 CrossRefPubMedGoogle Scholar
  35. 35.
    Huang X, Gao P, Song Y et al (2015) Meta-analysis of the prognostic value of circulating tumor cells detected with the cell search system in colorectal cancer. BMC Cancer 15:202. doi:10.1186/s12885-015-1218-9 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Rahbari NN, Aigner M, Thorlund K et al (2010) Meta-analysis shows that detection of circulating tumor cells indicates poor prognosis in patients with colorectal cancer. Gastroenterology 138:1714–1726. doi:10.1053/j.gastro.2010.01.008 CrossRefPubMedGoogle Scholar
  37. 37.
    Tol J, Koopman M, Miller MC et al (2010) Circulating tumour cells early predict progression-free and overall survival in advanced colorectal cancer patients treated with chemotherapy and targeted agents. Ann Oncol 21:1006–1012. doi:10.1093/annonc/mdp463 CrossRefPubMedGoogle Scholar
  38. 38.
    Cohen SJ, Punt CJA, Iannotti N et al (2008) Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol 26:3213–3221. doi:10.1200/JCO.2007.15.8923 CrossRefPubMedGoogle Scholar
  39. 39.
    Sastre J, Maestro ML, Gómez-España A et al (2012) Circulating tumor cell count is a prognostic factor in metastatic colorectal cancer patients receiving first-line chemotherapy plus bevacizumab: a Spanish Cooperative Group for the Treatment of Digestive Tumors study. Oncologist 17:947–955. doi:10.1634/theoncologist.2012-0048 CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Yokobori T, Iinuma H, Shimamura T et al (2013) Plastin3 is a novel marker for circulating tumor cells undergoing the epithelial-mesenchymal transition and is associated with colorectal cancer prognosis. Cancer Res 73:2059–2069. doi:10.1158/0008-5472.CAN-12-0326 CrossRefPubMedGoogle Scholar
  41. 41.
    Krebs MG, Renehan AG, Backen A et al (2015) Circulating tumor cell enumeration in a phase II trial of a four-drug regimen in advanced colorectal cancer. Clin Colorectal Cancer 14:115–122. doi:10.1016/j.clcc.2014.12.006 CrossRefPubMedGoogle Scholar
  42. 42.
    Vlaeminck-Guillem V (2015) When prostate cancer circulates in the bloodstream. Diagn Basel Switz 5:428–474. doi:10.3390/diagnostics5040428 Google Scholar
  43. 43.
    Scher HI, Heller G, Molina A et al (2015) Circulating tumor cell biomarker panel as an individual-level surrogate for survival in metastatic castration-resistant prostate cancer. J Clin Oncol 33:1348–1355. doi:10.1200/JCO.2014.55.3487 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Punnoose EA, Atwal S, Liu W et al (2012) Evaluation of circulating tumor cells and circulating tumor DNA in non-small cell lung cancer: association with clinical endpoints in a phase II clinical trial of pertuzumab and erlotinib. Clin Cancer Res 18:2391–2401. doi:10.1158/1078-0432.CCR-11-3148 CrossRefPubMedGoogle Scholar
  45. 45.
    Krebs MG, Sloane R, Priest L et al (2011) Evaluation and prognostic significance of circulating tumor cells in patients with non-small-cell lung cancer. J Clin Oncol 29:1556–1563. doi:10.1200/JCO.2010.28.7045 CrossRefPubMedGoogle Scholar
  46. 46.
    Hou J-M, Krebs MG, Lancashire L et al (2012) Clinical significance and molecular characteristics of circulating tumor cells and circulating tumor microemboli in patients with small-cell lung cancer. J Clin Oncol 30:525–532. doi:10.1200/JCO.2010.33.3716 CrossRefPubMedGoogle Scholar
  47. 47.
    Bidard F-C, Michiels S, et al (2016) IMENEO: International MEta-analysis of circulating tumor cell detection in early breast cancer patients treated by NEOadjuvant chemotherapy. In: Abstracts of the thirty-ninth annual CTRC-AACR San Antonio Breast Cancer Symposium, San Antonio, Texas, 6-10 December 2016. doi:10.1158/1538-7445.SABCS16-S3-01
  48. 48.
    Pierga J-Y, Bidard F-C, Autret A et al (2016) Circulating tumour cells and pathological complete response: independent prognostic factors in inflammatory breast cancer in a pooled analysis of two multicentre phase II trials (BEVERLY-1 and -2) of neoadjuvant chemotherapy combined with bevacizumab. Ann Oncol. doi:10.1093/annonc/mdw535 PubMedPubMedCentralGoogle Scholar
  49. 49.
    Rack B, Schindlbeck C, Jückstock J et al (2014) Circulating tumor cells predict survival in early average-to-high risk breast cancer patients. J Natl Cancer Inst. doi:10.1093/jnci/dju066 PubMedPubMedCentralGoogle Scholar
  50. 50.
    Scholten L, Terstappen LWMM, van der Palen J et al (2012) Circulating tumor cells as a possible prognostic tool in newly diagnosed nonmetastatic colorectal cancer? ASCO Meet Abstr 30:395Google Scholar
  51. 51.
    Iinuma H, Watanabe T, Mimori K et al (2011) Clinical significance of circulating tumor cells, including cancer stem-like cells, in peripheral blood for recurrence and prognosis in patients with Dukes’ stage B and C colorectal cancer. J Clin Oncol 29:1547–1555. doi:10.1200/JCO.2010.30.5151 CrossRefPubMedGoogle Scholar
  52. 52.
    Sotelo MJ, Sastre J, Maestro ML et al (2015) Role of circulating tumor cells as prognostic marker in resected stage III colorectal cancer. Ann Oncol 26:535–541. doi:10.1093/annonc/mdu568 CrossRefPubMedGoogle Scholar
  53. 53.
    Lu C-Y, Tsai H-L, Uen Y-H et al (2013) Circulating tumor cells as a surrogate marker for determining clinical outcome to mFOLFOX chemotherapy in patients with stage III colon cancer. Br J Cancer 108:791–797. doi:10.1038/bjc.2012.595 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Yoon SO, Kim YT, Jung KC et al (2011) TTF-1 mRNA-positive circulating tumor cells in the peripheral blood predict poor prognosis in surgically resected non-small cell lung cancer patients. Lung Cancer 71:209–216. doi:10.1016/j.lungcan.2010.04.017 CrossRefPubMedGoogle Scholar
  55. 55.
    Bayarri-Lara C, Ortega FG, de Guevara ACL et al (2016) Circulating tumor cells identify early recurrence in patients with non-small cell lung cancer undergoing radical resection. PLoS One 11:e0148659. doi:10.1371/journal.pone.0148659 CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Zhu W-F, Li J, Yu L-C et al (2014) Prognostic value of EpCAM/MUC1 mRNA-positive cells in non-small cell lung cancer patients. Tumour Biol 35:1211–1219. doi:10.1007/s13277-013-1162-8 CrossRefPubMedGoogle Scholar
  57. 57.
    Cabel L, Proudhon C, Mariani P et al (2017) Circulating tumor cells and circulating tumor DNA: what surgical oncologists need to know? Eur J Surg Oncol. doi:10.1016/j.ejso.2017.01.010 PubMedGoogle Scholar
  58. 58.
    Danila DC, Heller G, Gignac GA et al (2007) Circulating tumor cell number and prognosis in progressive castration-resistant prostate cancer. Clin Cancer Res 13:7053–7058. doi:10.1158/1078-0432.CCR-07-1506 CrossRefPubMedGoogle Scholar
  59. 59.
    Heidary M, Auer M, Ulz P et al (2014) The dynamic range of circulating tumor DNA in metastatic breast cancer. Breast Cancer Res 16:421. doi:10.1186/s13058-014-0421-y CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Tie J, Wang Y, Tomasetti C et al (2016) Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med 8:346ra92. doi:10.1126/scitranslmed.aaf6219 CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Cristofanilli M, Budd GT, Ellis MJ et al (2004) Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 351:781–791. doi:10.1056/NEJMoa040766 CrossRefPubMedGoogle Scholar
  62. 62.
    de Bono JS, Scher HI, Montgomery RB et al (2008) Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res 14:6302–6309. doi:10.1158/1078-0432.CCR-08-0872 CrossRefPubMedGoogle Scholar
  63. 63.
    Goldkorn A, Ely B, Quinn DI et al (2014) Circulating tumor cell counts are prognostic of overall survival in SWOG S0421: a phase III trial of docetaxel with or without atrasentan for metastatic castration-resistant prostate cancer. J Clin Oncol 32:1136–1142. doi:10.1200/JCO.2013.51.7417 CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Pearl ML, Dong H, Tulley S et al (2015) Treatment monitoring of patients with epithelial ovarian cancer using invasive circulating tumor cells (iCTCs). Gynecol Oncol 137:229–238. doi:10.1016/j.ygyno.2015.03.002 CrossRefPubMedGoogle Scholar
  65. 65.
    Ma J, Yao S, Li X-S et al (2015) Neoadjuvant therapy of dof regimen plus bevacizumab can increase surgical resection ratein locally advanced gastric cancer: a randomized controlled study. Medicine (Baltimore) 94:e1489. doi:10.1097/MD.0000000000001489 CrossRefGoogle Scholar
  66. 66.
    Zitt M, Zitt M, Müller HM et al (2006) Disseminated tumor cells in peripheral blood: a novel marker for therapy response in locally advanced rectal cancer patients undergoing preoperative chemoradiation. Dis Colon Rectum 49:1484–1491. doi:10.1007/s10350-006-0673-4 CrossRefPubMedGoogle Scholar
  67. 67.
    Kienle P, Koch M, Autschbach F et al (2003) Decreased detection rate of disseminated tumor cells of rectal cancer patients after preoperative chemoradiation: a first step towards a molecular surrogate marker for neoadjuvant treatment in colorectal cancer. Ann Surg 238:324–331. doi:10.1097/01.sla.0000086547.27615.e6 PubMedPubMedCentralGoogle Scholar
  68. 68.
    Gorges TM, Kuske A, Röck K et al (2016) Accession of tumor heterogeneity by multiplex transcriptome profiling of single circulating tumor cells. Clin Chem 62:1504–1515. doi:10.1373/clinchem.2016.260299 CrossRefPubMedGoogle Scholar
  69. 69.
    Bidard F-C, Pierga J-Y, Soria J-C et al (2013) Translating metastasis-related biomarkers to the clinic—progress and pitfalls. Nat Rev Clin Oncol 10:169–179. doi:10.1038/nrclinonc.2013.4 CrossRefPubMedGoogle Scholar
  70. 70.
    Smerage JB, Barlow WE, Hortobagyi GN et al (2014) Circulating tumor cells and response to chemotherapy in metastatic breast cancer: SWOG S0500. J Clin Oncol 32:3483–3489. doi:10.1200/JCO.2014.56.2561 CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Bidard F-C, Pierga J-Y (2015) Clinical utility of circulating tumor cells in metastatic breast cancer. J Clin Oncol 33:1622. doi:10.1200/JCO.2014.57.9714 CrossRefPubMedGoogle Scholar
  72. 72.
    Pestrin M, Bessi S, Puglisi F et al (2012) 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 134:283–289. doi:10.1007/s10549-012-2045-1 CrossRefPubMedGoogle Scholar
  73. 73.
    Stebbing J, Payne R, Reise J et al (2013) 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. doi:10.1371/journal.pone.0062543 Google Scholar
  74. 74.
    Georgoulias V, Bozionelou V, Agelaki S et al (2012) Trastuzumab decreases the incidence of clinical relapses in patients with early breast cancer presenting chemotherapy-resistant CK-19mRNA-positive circulating tumor cells: results of a randomized phase II study. Ann Oncol 23:1744–1750. doi:10.1093/annonc/mds020 CrossRefPubMedGoogle Scholar
  75. 75.
    Yu M, Bardia A, Wittner BS et al (2013) Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science 339:580–584. doi:10.1126/science.1228522 CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Aceto N, Bardia A, Miyamoto DT et al (2014) Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell 158:1110–1122. doi:10.1016/j.cell.2014.07.013 CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Mitra A, Mishra L, Li S (2015) EMT, CTCs and CSCs in tumor relapse and drug-resistance. Oncotarget 6:10697–10711CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Whittle JR, Lewis MT, Lindeman GJ et al (2015) Patient-derived xenograft models of breast cancer and their predictive power. Breast Cancer Res. doi:10.1186/s13058-015-0523-1 PubMedPubMedCentralGoogle Scholar
  79. 79.
    Agelaki S, Kalykaki A, Markomanolaki H et al (2015) Efficacy of lapatinib in therapy-resistant HER2-positive circulating tumor cells in metastatic breast cancer. PLoS One 10:e0123683. doi:10.1371/journal.pone.0123683 CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Hainsworth JD, Murphy PB, Alemar JR et al (2016) Use of a multiplexed immunoassay (PRO Onc assay) to detect HER2 abnormalities in circulating tumor cells of women with HER2-negative metastatic breast cancer: lack of response to HER2-targeted therapy. Breast Cancer Res Treat 160:41–49. doi:10.1007/s10549-016-3969-7 CrossRefPubMedGoogle Scholar

Copyright information

© Japan Society of Clinical Oncology 2017

Authors and Affiliations

  • Luc Cabel
    • 1
    • 2
  • Charlotte Proudhon
    • 2
  • Hugo Gortais
    • 1
  • Delphine Loirat
    • 1
    • 3
  • Florence Coussy
    • 1
  • Jean-Yves Pierga
    • 1
    • 2
    • 4
  • François-Clément Bidard
    • 1
    • 2
    • 5
  1. 1.Department of Medical Oncology, Institut CuriePSL Research UniversityParisFrance
  2. 2.Circulating Tumor Biomarkers Laboratory, SiRIC, Institut CuriePSL Research UniversityParisFrance
  3. 3.Translational Immunotherapy Team, SiRIC, Institut CuriePSL Research UniversityParisFrance
  4. 4.Paris Descartes UniversityParisFrance
  5. 5.Versailles-Saint-Quentin University, Paris-SaclaySaint CloudFrance

Personalised recommendations