Skip to main content
SpringerLink
Log in
Book cover

Breast Disease pp 191–199Cite as

Bone Marrow Micrometastases and Circulating Tumor Cells

  • Chapter
  • First Online:

Abstract

In clinical practice, although local recurrence or distant metastasis develops in some individuals who have been assessed as low risk despite treatment, some individuals with high-risk disease do not relapse despite systemic and local therapy. Therefore, oncologists need to determine objective prognostic factors to identify early recurrence and metastasis in patients with breast cancer. Based on the presumption of residual disease, clinicians have recently tried to identify micrometastases by using disseminated tumor cells (DTCs) in the bone marrow and circulating tumor cells (CTCs) from the peripheral blood. However, identifying the presence of DTCs and CTCs has required experienced staff and special laboratory. DTCs are known as epithelial cells in the bone marrow, and they are also considered micrometastases in the bone marrow. The morphological characteristics of DTCs include large cells with a large nucleus, nuclear granulation or stippling, strong or irregular staining for cytokeratin, and cytokeratin filaments. DTCs are observed in approximately 30% of early-stage breast cancer patients. Tumor cells circulating in the peripheral blood of patients with cancer are called CTCs. CTCs are cells that have entered the peripheral blood circulation after having detached from an existing primary tumor or its metastases. DTCs and CTCs can be used to predict progression-free and overall survival as well as response to treatment.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Available from.: http://www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-survival-by-stage. Date: 29.07.2018.

  2. Braun S, Vogl FD, Naume B, Janni W, Osborne MP, Coombes RC, et al. A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med. 2005;353(8):793–802.

    Article  CAS  PubMed  Google Scholar 

  3. Vincent-Salomon A, Bidard FC, Pierga JY. Bone marrow micrometastasis in breast cancer: review of detection methods, prognostic impact and biological issues. J Clin Pathol. 2008;61(5):570–6.

    Article  CAS  PubMed  Google Scholar 

  4. Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, et al. Expression of the 21 genes in the Recurrence Score assay and tamoxifen clinical benefit in the NSABP study B-14 of node negative, estrogen receptor positive breast cancer. J Clin Oncol. 2005;23(16_suppl):510.

    Article  Google Scholar 

  5. van de Vijver MJ, He YD, van’t Veer LJ, Dai H, Hart AA, Voskuil DW, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347(25):1999–2009.

    Article  PubMed  Google Scholar 

  6. Fehm T, Braun S, Muller V, Janni W, Gebauer G, Marth C, et al. A concept for the standardized detection of disseminated tumor cells in bone marrow from patients with primary breast cancer and its clinical implementation. Cancer. 2006;107(5):885–92.

    Article  PubMed  Google Scholar 

  7. Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S, et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2007;25(33):5287–312.

    Article  CAS  Google Scholar 

  8. Goldhirsch A, Ingle JN, Gelber RD, Coates AS, Thurlimann B, Senn HJ. Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2009. Ann Oncol Off J European Soc Med Oncol. 2009;20(8):1319–29.

    Article  CAS  Google Scholar 

  9. Naume B, Fehm T, Wiedswang G, Jückstock J, Borgen E, Rack B, et al. Persistence of isolated tumor cells in the bone marrow of breast cancer patients predicts increased risk for relapse – a European pooled analysis. Cancer Res. 2009;69(2 Supplement):304.

    Article  Google Scholar 

  10. Pierga JY, Bidard FC, Mathiot C, Brain E, Delaloge S, Giachetti S, et al. 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. 2008;14(21):7004–10.

    Article  CAS  PubMed  Google Scholar 

  11. Rack BK, Schindlbeck C, Schneeweiss A, Hilfrich J, Lorenz R, Beckmann MW, et al. Prognostic relevance of circulating tumor cells (CTCs) in peripheral blood of breast cancer patients before and after adjuvant chemotherapy: the German SUCCESS-trial. J Clin Oncol. 2008;26(15_suppl):503.

    Article  Google Scholar 

  12. Bidard FC, Vincent-Salomon A, Gomme S, Nos C, de Rycke Y, Thiery JP, et al. Disseminated tumor cells of breast cancer patients: a strong prognostic factor for distant and local relapse. Clin Cancer Res. 2008;14(11):3306–11.

    Article  CAS  PubMed  Google Scholar 

  13. Molino A, Giovannini M, Micciolo R, Auriemma A, Fiorio E, Santo A, et al. Bone marrow micrometastases in breast cancer patients: a long-term follow-up study. Clin Med Oncol. 2008;2:487–90.

    PubMed  PubMed Central  Google Scholar 

  14. Falck A-K, Bendahl P-O, Ingvar C, Isola J, Jönsson P-E, Lindblom P, et al. Analysis of and prognostic information from disseminated tumour cells in bone marrow in primary breast cancer: a prospective observational study. BMC Cancer. 2012;12:403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Hartkopf AD, Taran F-A, Wallwiener M, Hahn M, Becker S, Solomayer E-F, et al. Prognostic relevance of disseminated tumour cells from the bone marrow of early stage breast cancer patients – results from a large single-centre analysis. Eur J Cancer. 2014;50(15):2550–9.

    Article  PubMed  Google Scholar 

  16. Braun S, Pantel K, Muller P, Janni W, Hepp F, Kentenich CR, et al. Cytokeratin-positive cells in the bone marrow and survival of patients with stage I, II, or III breast cancer. N Engl J Med. 2000;342(8):525–33.

    Article  CAS  PubMed  Google Scholar 

  17. Diel IJ, Kaufmann M, Costa SD, Holle R, von Minckwitz G, Solomayer EF, et al. Micrometastatic breast cancer cells in bone marrow at primary surgery: prognostic value in comparison with nodal status. J Natl Cancer Inst. 1996;88(22):1652–8.

    Article  CAS  PubMed  Google Scholar 

  18. Braun S, Pantel K. Micrometastatic bone marrow involvement: detection and prognostic significance. Med Oncol (Northwood, London, England). 1999;16(3):154–65.

    Article  CAS  Google Scholar 

  19. Janni W, Vogl FD, Wiedswang G, Synnestvedt M, Fehm T, Juckstock J, et al. Persistence of disseminated tumor cells in the bone marrow of breast cancer patients predicts increased risk for relapse – a European pooled analysis. Clin Cancer Res. 2011;17(9):2967–76.

    Article  PubMed  Google Scholar 

  20. Naume B, Zhao X, Synnestvedt M, Borgen E, Russnes HG, Lingjaerde OC, et al. Presence of bone marrow micrometastasis is associated with different recurrence risk within molecular subtypes of breast cancer. Mol Oncol. 2007;1(2):160–71.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Muller V, Stahmann N, Riethdorf S, Rau T, Zabel T, Goetz A, et al. Circulating tumor cells in breast cancer: correlation to bone marrow micrometastases, heterogeneous response to systemic therapy and low proliferative activity. Clin Cancer Res. 2005;11(10):3678–85.

    Article  PubMed  Google Scholar 

  22. Pierga JY, Bonneton C, Vincent-Salomon A, de Cremoux P, Nos C, Blin N, et al. Clinical significance of immunocytochemical detection of tumor cells using digital microscopy in peripheral blood and bone marrow of breast cancer patients. Clin Cancer Res. 2004;10(4):1392–400.

    Article  CAS  PubMed  Google Scholar 

  23. Fehm T, Becker S, Becker-Pergola G, Sotlar K, Gebauer G, Dürr-Störzer S, et al. Presence of apoptotic and nonapoptotic disseminated tumor cells reflects the response to neoadjuvant systemic therapy in breast cancer. Breast Cancer Res. 2006;8(5):R60-R.

    Article  CAS  Google Scholar 

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

    Google Scholar 

  25. Lianidou ES, Strati A, Markou A. Circulating tumor cells as promising novel biomarkers in solid cancers. Crit Rev Clin Lab Sci. 2014;51(3):160–71.

    Article  CAS  PubMed  Google Scholar 

  26. Lianidou ES, Mavroudis D, Georgoulias V. Clinical challenges in the molecular characterization of circulating tumour cells in breast cancer. Br J Cancer. 2013;108(12):2426–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Lianidou ES, Markou A, Strati A. Molecular characterization of circulating tumor cells in breast cancer: challenges and promises for individualized cancer treatment. Cancer Metastasis Rev. 2012;31(3–4):663–71.

    Article  CAS  PubMed  Google Scholar 

  28. Parkinson DR, Dracopoli N, Petty BG, Compton C, Cristofanilli M, Deisseroth A, et al. Considerations in the development of circulating tumor cell technology for clinical use. J Transl Med. 2012;10:138.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Cabel L, Proudhon C, Gortais H, Loirat D, Coussy F, Pierga JY, et al. Circulating tumor cells: clinical validity and utility. Int J Clin Oncol. 2017;22(3):421–30.

    Article  PubMed  Google Scholar 

  30. 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(8):781–91.

    Article  CAS  PubMed  Google Scholar 

  31. Cohen SJ, Alpaugh RK, Gross S, O’Hara SM, Smirnov DA, Terstappen LW, et al. Isolation and characterization of circulating tumor cells in patients with metastatic colorectal cancer. Clin Colorectal Cancer. 2006;6(2):125–32.

    Article  CAS  PubMed  Google Scholar 

  32. Okegawa T, Nutahara K, Higashihara E. Prognostic significance of circulating tumor cells in patients with hormone refractory prostate cancer. J Urol. 2009;181(3):1091–7.

    Article  PubMed  Google Scholar 

  33. 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(5):463–74.

    Article  CAS  PubMed  Google Scholar 

  34. 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(10):3970–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Allan AL, Keeney M. Circulating tumor cell analysis: technical and statistical considerations for application to the clinic. J Oncol. 2010;2010:426218.

    Article  PubMed  Google Scholar 

  36. Muller V, Riethdorf S, Rack B, Janni W, Fasching PA, Solomayer E, et al. Prognostic impact of circulating tumor cells assessed with the CellSearch System and AdnaTest Breast in metastatic breast cancer patients: the DETECT study. Breast Cancer Res. 2012;14(4):R118.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Punnoose EA, Atwal SK, Spoerke JM, Savage H, Pandita A, Yeh RF, et al. Molecular biomarker analyses using circulating tumor cells. PLoS One. 2010;5(9):e12517.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Aktas B, Kasimir-Bauer S, Muller V, Janni W, Fehm T, Wallwiener D, et al. Comparison of the HER2, estrogen and progesterone receptor expression profile of primary tumor, metastases and circulating tumor cells in metastatic breast cancer patients. BMC Cancer. 2016;16:522.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. 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(2):356–60.

    Article  CAS  PubMed  Google Scholar 

  40. Beije N, Onstenk W, Kraan J, Sieuwerts AM, Hamberg P, Dirix LY, et al. Prognostic Impact of HER2 and ER Status of Circulating Tumor Cells in Metastatic Breast Cancer Patients with a HER2-Negative Primary Tumor. Neoplasia (New York, NY). 2016;18(11):647–53.

    Article  CAS  Google Scholar 

  41. Ramos-Medina R, Moreno F, Lopez-Tarruella S, Del Monte-Millan M, Marquez-Rodas I, Duran E, et al. Review: circulating tumor cells in the practice of breast cancer oncology. Clin Transl Oncol. 2016;18(8):749–59.

    Article  CAS  PubMed  Google Scholar 

  42. Xenidis N, Perraki M, Kafousi M, Apostolaki S, Bolonaki I, Stathopoulou A, et al. Predictive and prognostic value of peripheral blood cytokeratin-19 mRNA-positive cells detected by real-time polymerase chain reaction in node-negative breast cancer patients. J Clin Oncol. 2006;24(23):3756–62.

    Article  CAS  PubMed  Google Scholar 

  43. Ignatiadis M, Xenidis N, Perraki M, Apostolaki S, Politaki E, Kafousi M, et al. Different prognostic value of cytokeratin-19 mRNA positive circulating tumor cells according to estrogen receptor and HER2 status in early-stage breast cancer. J Clin Oncol. 2007;25(33):5194–202.

    Article  PubMed  Google Scholar 

  44. Rack BK, Schindlbeck C, Andergassen U, Schneeweiss A, Zwingers T, Lichtenegger W, et al. Use of circulating tumor cells (CTC) in peripheral blood of breast cancer patients before and after adjuvant chemotherapy to predict risk for relapse: the SUCCESS trial. J Clin Oncol. 2010;28(15_suppl):1003.

    Article  Google Scholar 

  45. Bidard FC, Mathiot C, Delaloge S, Brain E, Giachetti S, de Cremoux P, et al. Single circulating tumor cell detection and overall survival in nonmetastatic breast cancer. Ann Oncol. 2010;21(4):729–33.

    Article  PubMed  Google Scholar 

  46. Franken B, de Groot MR, Mastboom WJ, Vermes I, van der Palen J, Tibbe AG, et al. Circulating tumor cells, disease recurrence and survival in newly diagnosed breast cancer. Breast Cancer Res. 2012;14(5):R133.

    Article  PubMed  PubMed Central  Google Scholar 

  47. 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(7):688–95.

    Article  PubMed  Google Scholar 

  48. Hall CS, Karhade MG, Bowman Bauldry JB, Valad LM, Kuerer HM, DeSnyder SM, et al. Prognostic value of circulating tumor cells identified before surgical resection in nonmetastatic breast cancer patients. J Am Coll Surg. 2016;223(1):20–9.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Riethdorf S, Muller V, Loibl S, Nekljudova V, Weber K, Huober J, et al. Prognostic impact of circulating tumor cells for breast cancer patients treated in the neoadjuvant “Geparquattro” trial. Clin Cancer Res. 2017;23(18):5384–93.

    Article  CAS  PubMed  Google Scholar 

  50. Hayes DF, Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Miller MC, et al. Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival. Clin Cancer Res. 2006;12(14 Pt 1):4218–24.

    Article  CAS  PubMed  Google Scholar 

  51. 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(3):R67.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Giordano A, Cristofanilli M. CTCs in metastatic breast cancer. Recent Results Cancer Res. 2012;195:193–201.

    Article  PubMed  Google Scholar 

  53. 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(3):618–24.

    Article  PubMed  Google Scholar 

  54. 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(2):503–10.

    Article  PubMed  Google Scholar 

  55. Jiang ZF, Cristofanilli M, Shao ZM, Tong ZS, Song EW, Wang XJ, et al. Circulating tumor cells predict progression-free and overall survival in Chinese patients with metastatic breast cancer, HER2-positive or triple-negative (CBCSG004): a multicenter, double-blind, prospective trial. Ann Oncol. 2013;24(11):2766–72.

    Article  CAS  PubMed  Google Scholar 

  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;32(31):3483–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Wallwiener M, Riethdorf S, Hartkopf AD, Modugno C, Nees J, Madhavan D, et al. Serial enumeration of circulating tumor cells predicts treatment response and prognosis in metastatic breast cancer: a prospective study in 393 patients. BMC Cancer. 2014;14:512.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Giuliano M, Giordano A, Jackson S, De Giorgi U, Mego M, Cohen EN, et al. Circulating tumor cells as early predictors of metastatic spread in breast cancer patients with limited metastatic dissemination. Breast Cancer Res. 2014;16(5):440.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. 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(6):560–7.

    Article  PubMed  Google Scholar 

  60. Yan WT, Cui X, Chen Q, Li YF, Cui YH, Wang Y, et al. Circulating tumor cell status monitors the treatment responses in breast cancer patients: a meta-analysis. Sci Rep. 2017;7:43464.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Krishnamurthy S, Cristofanilli M, Singh B, Reuben J, Gao H, Cohen EN, et al. Detection of minimal residual disease in blood and bone marrow in early stage breast cancer. Cancer. 2010;116(14):3330–7.

    Article  PubMed  Google Scholar 

  62. Riethdorf S, Muller 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 Off J Am Assoc Cancer Res. 2010;16(9):2634–45.

    Article  CAS  Google Scholar 

  63. Xenidis N, Markos V, Apostolaki S, Perraki M, Pallis A, Sfakiotaki G, et al. Clinical relevance of circulating CK-19 mRNA-positive cells detected during the adjuvant tamoxifen treatment in patients with early breast cancer. Ann Oncol. 2007;18(10):1623–31.

    Article  CAS  PubMed  Google Scholar 

  64. Xenidis N, Ignatiadis M, Apostolaki S, Perraki M, Kalbakis K, Agelaki S, et al. Cytokeratin-19 mRNA-positive circulating tumor cells after adjuvant chemotherapy in patients with early breast cancer. J Clin Oncol. 2009;27(13):2177–84.

    Article  CAS  PubMed  Google Scholar 

  65. Saloustros E, Perraki M, Apostolaki S, Kallergi G, Xyrafas A, Kalbakis K, et al. Cytokeratin-19 mRNA-positive circulating tumor cells during follow-up of patients with operable breast cancer: prognostic relevance for late relapse. Breast Cancer Res. 2011;13(3):R60.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Sandri MT, Zorzino L, Cassatella MC, Bassi F, Luini A, Casadio C, et al. Changes in circulating tumor cell detection in patients with localized breast cancer before and after surgery. Ann Surg Oncol. 2010;17(6):1539–45.

    Article  PubMed  Google Scholar 

  67. Biggers B, Knox S, Grant M, Kuhn J, Nemunatitis J, Fisher T, et al. Circulating tumor cells in patients undergoing surgery for primary breast cancer: preliminary results of a pilot study. Ann Surg Oncol. 2009;16(4):969–71.

    Article  PubMed  Google Scholar 

  68. Fehm T, Muller V, Aktas B, Janni W, Schneeweiss A, Stickeler E, et al. HER2 status of circulating tumor cells in patients with metastatic breast cancer: a prospective, multicenter trial. Breast Cancer Res Treat. 2010;124(2):403–12.

    Article  CAS  PubMed  Google Scholar 

  69. Untch M, Loibl S, Bischoff J, Eidtmann H, Kaufmann M, Blohmer JU, et al. Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomised phase 3 trial. Lancet Oncol. 2012;13(2):135–44.

    Article  CAS  PubMed  Google Scholar 

  70. Bidard F-C, 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  PubMed Central  Google Scholar 

  71. Fei F, Du Y, Di G, Wu J, Shao Z. Are changes in circulating tumor cell (CTC) count associated with the response to neoadjuvant chemotherapy in local advanced breast cancer? A meta-analysis. Oncol Res Treat. 2014;37(5):250–4.

    Article  CAS  PubMed  Google Scholar 

  72. 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(9):2422–30.

    Article  PubMed  Google Scholar 

  73. 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(20):5701–10.

    Article  PubMed  Google Scholar 

  74. Giordano A, Egleston BL, Hajage D, Bland J, Hortobagyi GN, Reuben JM, et al. Establishment and validation of circulating tumor cell-based prognostic nomograms in first-line metastatic breast cancer patients. Clin Cancer Res. 2013;19(6):1596–602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Martin M, Custodio S, de Las Casas ML, Garcia-Saenz JA, de la Torre JC, Bellon-Cano JM, et al. Circulating tumor cells following first chemotherapy cycle: an early and strong predictor of outcome in patients with metastatic breast cancer. The oncologist. 2013;18(8):917–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Budd GT, Cristofanilli M, Ellis MJ, Stopeck A, Borden E, Miller MC, et al. Circulating tumor cells versus imaging – predicting overall survival in metastatic breast cancer. Clin Cancer Res. 2006;12(21):6403–9.

    Article  CAS  PubMed  Google Scholar 

  77. 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(5):1144–50.

    Article  CAS  PubMed  Google Scholar 

  78. Giordano A, Giuliano M, Handy B, Ueno N, Alvarez R, Cohen E, et al. Abstract PD04-02: clinical value of circulating tumor cells (CTC) in first line metastatic breast cancer (MBC) patients (pts) according to type of treatment and immunohistochemical molecular subtype. Cancer Res. 2010;70(24 Supplement):PD04-2-PD-2.

    Article  Google Scholar 

  79. 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(31):5153–9.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Pierga JY, Bidard FC, Cropet C, Tresca P, Dalenc F, Romieu G, et al. Circulating tumor cells and brain metastasis outcome in patients with HER2-positive breast cancer: the LANDSCAPE trial. Ann Oncol. 2013;24(12):2999–3004.

    Article  PubMed  Google Scholar 

  81. Rack B, Schindlbeck C, Juckstock 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.

    Article  Google Scholar 

  82. Castro-Giner F, Gkountela S, Donato C, Alborelli I, Quagliata L, Ng CKY, et al. Cancer diagnosis using a liquid biopsy: challenges and expectations. Diagnostics. 2018;8(2):31.

    Article  PubMed Central  Google Scholar 

  83. Alix-Panabieres C, Pantel K. Circulating tumor cells: liquid biopsy of cancer. Clin Chem. 2013;59(1):110–8.

    Article  CAS  PubMed  Google Scholar 

  84. Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014;6(224):224ra24-ra24.

    Article  CAS  Google Scholar 

  85. Dawson SJ, Tsui DW, Murtaza M, Biggs H, Rueda OM, Chin SF, et al. Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med. 2013;368(13):1199–209.

    Article  CAS  PubMed  Google Scholar 

  86. Madhavan D, Wallwiener M, Bents K, Zucknick M, Nees J, Schott S, et al. Plasma DNA integrity as a biomarker for primary and metastatic breast cancer and potential marker for early diagnosis. Breast Cancer Res Treat. 2014;146(1):163–74.

    Article  CAS  PubMed  Google Scholar 

  87. Yang J, Cheng L, Zhang J, Chen L, Wang D, Guo X, et al. Predictive value of circulating cell-free DNA in the survival of breast cancer patients: A systemic review and meta-analysis. Medicine. 2018;97(28):e11417.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkey

    Saadettin Kilickap, Burak Yasin Aktas & Y. Yavuz Ozisik

Authors
  1. Saadettin Kilickap
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Burak Yasin Aktas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Y. Yavuz Ozisik
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Medical Oncology, Istanbul Medical Faculty, Oncology Institute, Istanbul University, Istanbul, Turkey

    Adnan Aydiner

  2. Department of General Surgery, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey

    Abdullah Igci

  3. Department of Surgical Oncology, Magee-Womens Hospital of the University of Pittsburgh, Pittsburgh, PA, USA

    Atilla Soran

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Kilickap, S., Aktas, B.Y., Ozisik, Y.Y. (2019). Bone Marrow Micrometastases and Circulating Tumor Cells. In: Aydiner, A., Igci, A., Soran, A. (eds) Breast Disease. Springer, Cham. https://doi.org/10.1007/978-3-030-04606-4_13

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-04606-4_13

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-04605-7

  • Online ISBN: 978-3-030-04606-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation