Download PDF
CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd 2017; 77(12): 1291-1298
DOI: 10.1055/s-0043-122884
GebFra Science
Review/Übersicht
Georg Thieme Verlag KG Stuttgart · New York

Circulating Tumour Cells, Circulating Tumour DNA and Circulating MicroRNA in Metastatic Breast Carcinoma – What is the Role of Liquid Biopsy in Breast Cancer?

Article in several languages: English | deutsch
Arkadius Polasik
1   Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum Ulm, Ulm, Germany
,
Marie Tzschaschel
1   Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum Ulm, Ulm, Germany
,
Fabienne Schochter
1   Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum Ulm, Ulm, Germany
,
Amelie de Gregorio
1   Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum Ulm, Ulm, Germany
,
Thomas W. P. Friedl
1   Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum Ulm, Ulm, Germany
,
Brigitte Rack
1   Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum Ulm, Ulm, Germany
,
Andreas Hartkopf
2   Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum Tübingen, Tübingen, Germany
,
Peter A. Fasching
3   Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum Erlangen, Erlangen, Germany
,
Andreas Schneeweiss
4   Nationales Centrum für Tumorerkrankungen, Universitätsklinikum Heidelberg, Heidelberg, Germany
,
Volkmar Müller
5   Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
,
Jens Huober
1   Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum Ulm, Ulm, Germany
,
Wolfgang Janni
1   Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum Ulm, Ulm, Germany
,
Tanja Fehm
6   Klinik für Gynäkologie und Geburtshilfe, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany
› Author Affiliations
Further Information

Publication History

received 16 July 2017
revised 09 November 2017

accepted 12 November 2017

Publication Date:
18 December 2017 (online)

Also available at
   Permissions and Reprints

Abstract

Dissemination of tumour cells and the development of solid metastases occurs via blood vessels and lymphatics. Circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA) can be detected in venous blood in patients with early and metastatic breast cancer, and their prognostic relevance has been demonstrated on numerous occasions. Repeated testing for CTCs and ctDNA, or regular so-called “liquid biopsy”, can be performed easily at any stage during the course of disease. Additional molecular analysis allows definition of tumour characteristics and heterogeneity that may be associated with treatment resistance. This in turn makes personalised, targeted treatments possible that may achieve both improved overall survival and quality of life.

Key words

breast - Her-2/neu (human epidermal growth factor recptor) - hormonal receptor - mammary gland tumor - metastasis
 

  • References/Literatur

  • 1 Aktuelle Empfehlungen zur Diagnostik und Therapie primärer und metastasierter Mammakarzinome der Kommission MAMMA in der AGO e.V.. 2017 Online: http://www.ago-online.de last access: 09/2017
    PubMedGoogle Scholar
  • 2 Gerlinger M, Rowan AJ, Horswell S. et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 2012; 366: 883-892
    CrossrefPubMedGoogle Scholar
  • 3 Paget S. The distribution of secondary growth in cancer of the breast. Lancet 1889; 133: 571-573
    CrossrefPubMedGoogle Scholar
  • 4 Braun S, Vogl FD, Naume B. et al. A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med 2005; 353: 793-802
    CrossrefPubMedGoogle Scholar
  • 5 Janni W, Vogl FD, Wiedswang G. 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: 2967-2976
    CrossrefPubMedGoogle Scholar
  • 6 Fehm T, Muller V, Aktas B. et al. HER2 status of circulating tumor cells in patients with metastatic breast cancer: a prospective, multicenter trial. Breast Cancer Res Treat 2010; 124: 403-412
    CrossrefPubMedGoogle Scholar
  • 7 Bidard F-C, Peeters DJ, Fehm T. et al. Clinical validity of circulating tumor cells in patients with metastatic breast cancer: a pooled analysis of individual patient data. Lancet Oncol 2015; 15: 406-415
    PubMedGoogle Scholar
  • 8 Müller V, Riethdorf S, Rack B. 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: R118
    CrossrefPubMedGoogle Scholar
  • 9 Bidard FC, Peeters DJ, Fehm T. 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: 406-414
    CrossrefPubMedGoogle Scholar
  • 10 Rack B, Schindlbeck C, Jückstock J. et al. Circulating tumor cells predict survival in early average-to-high risk breast cancer patients. J Natl Cancer Inst 2014; 106: pii:dju066 doi:10.1093/jnci/dju066
    PubMedGoogle Scholar
  • 11 Janni W, Rack B, Terstappen LW. et al. Pooled analysis of the prognostic relevance of circulating tumor cells in primary breast cancer. Clin Cancer Res 2016; 22: 2583-2593
    CrossrefPubMedGoogle Scholar
  • 12 Yang YF, Liao YY, Yang M. et al. Discordances in ER, PR and HER2 receptors between primary and recurrent/metastatic lesions and their impact on survival in breast. Med Oncol 2014; 31: 214
    CrossrefPubMedGoogle Scholar
  • 13 Heitz F, Barinoff J, du Bois O. et al. Differences in the receptor status between primary and recurrent breast cancer – the frequency of and the reasons for discordance. Oncology 2013; 84: 319-325
    CrossrefPubMedGoogle Scholar
  • 14 Somlo G, Lau SK, Frankel P. et al. Multiple biomarker expression on circulating tumor cells in comparison to tumor tissues from primary and metastatic sites in patients with locally advanced/inflammatory, and stage IV breast cancer, using a novel detection technology. Breast Cancer Res Treat 2011; 128: 155-163
    CrossrefPubMedGoogle Scholar
  • 15 Munzone E, Nolé F, Goldhirsch A. 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: 392-397
    CrossrefPubMedGoogle Scholar
  • 16 Jäger BA, Finkenzeller C, Bock C. et al. Estrogen receptor and HER2 status on disseminated tumor cells and primary tumor in patients with early breast cancer. Transl Oncol 2015; 8: 509-516
    CrossrefPubMedGoogle Scholar
  • 17 Santinelli A, Pisa E, Stramazzotti D. et al. HER-2 status discrepancy between primary breast cancer and metastatic sites. Impact on target therapy. Int J Cancer 2008; 122: 999-1004
    PubMedGoogle Scholar
  • 18 Schramm A, Friedl TWP, Schochter F. et al. Association between HER2-phenotype on circulation tumor cells and primary tumor characteristics in women with metastatic breast cancer. AscoAnnuMeet 2015; 51: 266
    PubMedGoogle Scholar
  • 19 Hanf V, Schütz F, Liedtke C. et al. AGO recommendations for the diagnosis and treatment of patients with advanced and metastatic breast cancer: Update. Breast Care (Basel) 2014; 9: 202-209
    CrossrefPubMedGoogle Scholar
  • 20 Paoletti C. Abstract OT1-3-01: Characterization of circulating tumor cells from subjects with metastatic breast cancer using the CTC-endocrine therapy index: the COMETI-P2-2012.0 trial. Cancer Res 2013; 73 (24 Suppl.): OT1-3-01
    CrossrefPubMedGoogle Scholar
  • 21 Online: http://www.clinicaltrials.gov/ct2/show/NCT01349842 last access: 09/2017
    PubMed
  • 22 Smerage JB, Barlow WE, Hortobagyi GN. et al. Circulating tumor cells and response to chemotherapy in metastatic breast cancer: SWOG S0500. J Clin Oncol 2014; 32: 3483-3489
    CrossrefPubMedGoogle Scholar
  • 23 Online: http://www.clinicaltrials.gov/ct2/show/NCT01710605 last access: 09/2017
    PubMed
  • 24 Kataoka Y, Mukohara T, Shimada H. et al. Association between gain-of-function mutations in PIK3CA and resistance to HER2-targeted agents in HER2-amplified breast cancer cell lines. Ann Oncol 2010; 21: 255-262
    CrossrefPubMedGoogle Scholar
  • 25 Eichhorn PJA, Gili M, Scaltriti M. et al. Phosphatidyinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ235. Cancer Res 2008; 68: 9221-9230
    CrossrefPubMedGoogle Scholar
  • 26 Dupont Jensen J, Laenkholm AV, Knoop A. et al. PIK3CA mutations may be discordant between primary and corresponding metastatic disease in breast cancer. Clin Cancer Res 2011; 17: 667-677
    CrossrefPubMedGoogle Scholar
  • 27 Mandel PM. Les acides nucleiques du plasma sanguin chez lʼhomme. CR Acad Sci Paris 1940; 142: 241-253
    PubMedGoogle Scholar
  • 28 Casciano I, Vinci AD, Banelli B. et al. Circulating tumor nucleic acids: perspective in breast cancer. Breast Care (Basel) 2010; 5: 75-80
    CrossrefPubMedGoogle Scholar
  • 29 Lo YM, Rainer TH, Chan LY. et al. Plasma DNA as a prognostic marker in trauma patients. Clin Chem 2000; 46: 319-323
    PubMedGoogle Scholar
  • 30 Sozzi G, Conte D, Leon M. et al. Quantification of free circulating DNA as a diagnostic marker in lung cancer. J Clin Oncol 2003; 21: 3902-3908
    CrossrefPubMedGoogle Scholar
  • 31 Leon SA, Shapiro B, Sklaroff DM. et al. Free DNA in the serum of cancer patients and the effect of therapy. Cancer Res 1977; 37: 646-650
    PubMedGoogle Scholar
  • 32 Bettegowda C, Sausen M, Leary RJ. et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med 2014; 6: 22ra224
    CrossrefPubMedGoogle Scholar
  • 33 Dawson SJ, Rosenfeld N, Caldas C. Circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med 2013; 369: 93-94
    CrossrefPubMedGoogle Scholar
  • 34 Heidary M, Auer M, Ulz P. et al. The dynamic range of circulating tumor DNA in metastatic breast cancer. Breast Cancer Res 2014; 16: 421
    CrossrefPubMedGoogle Scholar
  • 35 Madic J, Kiialainen A, Bidard FC. et al. Circulating tumor DNA and circulating tumor cells in metastatic triple negative breast cancer patients. Int J Cancer 2015; 136: 2158-2165
    CrossrefPubMedGoogle Scholar
  • 36 Board RE, Wardley AM, Dixon JM. et al. Detection of PIK3CA mutations in circulating free DNA in patients with breast cancer. Breast Cancer Res Treat 2010; 120: 461-467
    CrossrefPubMedGoogle Scholar
  • 37 Baselga J, Im SA, Iwata H. et al. PIK3CA status in circulating tumor DNA (ctDNA) predicts efficacy of buparlisib (BUP) plus fulvestrant (FULV) in postmenopausal women with endocrine-resistant HR+/HER2– advanced breast cancer (BC): first results from the randomized, phase III BELLE-2 trial. San Antonio Breast Cancer Symposium 2015; San Antonio, TX, USA; Abstract S6-01.
    PubMedGoogle Scholar
  • 38 Di Leo A, Ciruelos E, Janni W. et al. BELLE-3: A phase III study of the pan-phosphatidylinositol 3-kinase (PI3K) inhibitor buparlisib (BKM120) with fulvestrant in postmenopausal women with HR+/HER2- locally advanced/metastatic breast cancer (BC) pretreated with aromatase inhibitors (AIs) and refractory to mTOR inhibitor (mTORi)-based treatment. ASCO Annual Meeting 2015; Chicago, Il; Abstract TPS626.
    PubMedGoogle Scholar
  • 39 Di Leo A, Seok Lee K, Ciruelos E. BELLE-3: a phase III study of buparlisib + fulvestrant in postmenopausal women with HR+, HER2–, aromatase inhibitor-treated, locally advanced or metastatic breast cancer, who progressed on or after mTOR inhibitor-based treatment. San Antonio Breast Cancer Symposium 2016; San Antonio, TX, USA; Abstract S4-07.
    PubMedGoogle Scholar
  • 40 Yager JD, Davidson NE. Estrogen carcinogenesis in breast cancer. N Engl J Med 2006; 354: 270-282
    CrossrefPubMedGoogle Scholar
  • 41 Merenbakh-Lamin K, Ben-Baruch N, Yeheskel A. et al. D538 G mutation in estrogen receptor-alpha: a novel mechanism for acquired endocrine resistance in breast cancer. Cancer Res 2013; 73: 6856-6864
    CrossrefPubMedGoogle Scholar
  • 42 Toy W, Shen Y, Won H. et al. ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat Genet 2013; 45: 1439-1445
    CrossrefPubMedGoogle Scholar
  • 43 Wang P, Bahreini A, Gyanchandani R. et al. Sensitive detection of mono- and polyclonal ESR1 mutations in primary tumors, metastatic lesions and cell free DNA of breast cancer patients. Clin Cancer Res 2016; 22: 1130-1137
    CrossrefPubMedGoogle Scholar
  • 44 Chandarlapaty S, Chen D, He W. et al. Prevalence of ESR1 mutations in cell-free DNA and outcomes in metastatic breast cancer: a secondary analysis of the BOLERO-2 clinical trial. JAMA Oncol 2016; 2: 1310-1315
    CrossrefPubMedGoogle Scholar
  • 45 Ma F, Zhu W, Guan Y. et al. ctDNA dynamics: a novel indicator to track resistance in metastatic breast cancer treated with anti-HER2 therapy. Oncotarget 2016; 7: 66020-66031
    PubMedGoogle Scholar
  • 46 Fasching PA, Brucker SY, Fehm TN. et al. Biomarkers in patients with metastatic breast cancer and the PRAEGNANT study network. Geburtsh Frauenheilk 2015; 75: 41-50
    Article in Thieme ConnectPubMedGoogle Scholar
  • 47 Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993; 75: 843-854
    CrossrefPubMedGoogle Scholar
  • 48 Roth C, Rack B, Muller V. et al. Circulating microRNAs as blood-based markers for patients with primary and metastatic breast cancer. Breast Cancer Res 2010; 12: R90
    CrossrefPubMedGoogle Scholar
  • 49 Madhavan D, Peng C, Wallwiener M. et al. Circulating miRNAs with prognostic value in metastatic breast cancer and for early detection of metastasis. Carcinogenesis 2016; 37: 461-470
    CrossrefPubMedGoogle Scholar