Skip to main content

Advertisement

SpringerLink
Log in

Sustained prognostic impact of circulating tumor cell status and kinetics upon further progression of metastatic breast cancer

  • Clinical trial
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

Serial longitudinal enumeration of circulating tumor cells (CTCs) has shown its prognostic value on progression-free survival and overall survival (OS) in patients with stage IV breast cancer. This study prospectively evaluated the role of CTCs as a prognostic marker during further progression of metastatic breast cancer (MBC).

Methods

Among 476 MBC patients recruited between 2010 and 2015, the 103 patients with a known CTC status at baseline (CTCBL) and within 4 weeks of tumor progression (CTCPD) were included. Progressive disease (PD) was defined according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Using the CellSearch method, < 5 and ≥ 5 CTCs per 7.5 ml blood were determined as negative and positive, respectively. A shift in CTC status from baseline to progression (\({\text {CTC}_\text {BL}}^+\) to \({\text {CTC}_\text {PD}}^-\) and vice versa) was considered as alternating KineticsBL–PD.

Results

Median follow-up was 29.9 [21.2, 40.0] months. CTCPD positivity (37%, n = 38) was associated with a significantly shorter OS than CTCPD negativity (8.0 [5.1, 10.9] vs 22.6 [15.3, 39.8] months; P < 0.001). Alternating KineticsBL–PD was observed in 24% of the patients. This significantly changed the OS prediction of \({\text {CTC}_\text {BL}}^+\) patients (\({{\text {CTC}_\text {BL}}^+}{{\text {CTC}_\text {PD}}^-}\) vs \({{\text {CTC}_\text {BL}}^+}{{\text {CTC}_\text {PD}}^+}\), 11.4 [9.7, not available (NA)] vs. 7.6 [4.4, 11.5] months; P = 0.044) and \({\text {CTC}_\text {BL}}^-\) patients (\({{\text {CTC}_\text {BL}}^-}{{\text {CTC}_\text {PD}}^+}\) vs. \({{\text {CTC}_\text {BL}}^-}{{\text {CTC}_\text {PD}}^-}\), 8.4 [4.0, NA] vs. 22.6 [18.9, NA] months, respectively; P < 0.001).

Prediction of survival was significantly improved (P = 0.002) by adding CTCPD status to clinicopathological characteristics and CTCBL status.

Conclusions

CTC status upon further disease progression is a prognostic factor that could significantly improve well-established models. Thus, it represents a potential additional instrument supporting treatment decision.

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
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

MBC:

Metastatic breast cancer

CTCs:

Circulating tumor cells

PFS:

Progression-free survival

OS:

Overall survival

CEA:

Carcinoembryonic antigen

CA15-3:

Cancer antigen 15-3

iCTCs:

Intact circulating tumor cells

aCTCs:

Apoptotic circulating tumor cells

fCTCs:

Enucleated fragments of circulating tumor cells

NCT:

National Center for Tumor Diseases

REMARK:

Reporting recommendations for tumor marker prognostic studies

RECIST:

Response Evaluation Criteria in Solid Tumors

SD:

Stable disease

PR:

Partial response

CR:

Complete response

PD:

Progressive disease

BL:

Baseline/study inclusion

CTCBL :

CTC status at baseline

CTCPD :

CTC status within 4 weeks of tumor progression

FDA:

US Food and Drug Administration

anti-EpCAM:

Anti-epithelial cellular adhesion molecule antibody

DAPI:

4,2-Diamidino-2-phenylindole

\({\text {CTC}_\text {BL}}^-/{\text {CTC}_\text {BL}}^+\) :

Negative/positive CTC status at baseline

\({\text {CTC}_\text {PD}}^-/{\text {CTC}_\text {PD}}^+\) :

Negative/positive CTC status within 4 weeks of tumor progression

iKineticsBL–PD :

Course of intact CTCs from BL to PD

aKineticsBL–PD :

Course of apoptotic CTCs from BL to PD

fKineticsBL–PD :

Course of enucleated fragments of CTCs from BL to PD

\({\text {Kinetics}_\text {BL-PD}}^{-/+}\) :

\({\text {CTC}_\text {BL}}^-\) to \({\text {CTC}_\text {PD}}^+\)

\({\text {Kinetics}_\text {BL-PD}}^{+/-}\) :

\({\text {CTC}_\text {BL}}^+\) to \({\text {CTC}_\text {PD}}^-\)

\({\text {Kinetics}_\text {BL-PD}}^{+/+}\) :

\({\text {CTC}_\text {BL}}^+\) to \({\text {CTC}_\text {PD}}^+\)

\({\text {Kinetics}_\text {BL-PD}}^{-/-}\) :

\({\text {CTC}_\text {BL}}^-\) to \({\text {CTC}_\text {PD}}^-\)

r s :

Spearman correlation coefficient

CI:

Confidence interval

BIC:

Bayesian information criterion

HR:

Hormone receptor or hazard ratio

HER2:

Human epidermal growth factor receptor 2

ER:

Estrogen receptor

PR:

Progesterone receptor

TNBC:

Triple-negative breast cancer

ctDNA:

Circulating tumor DNA

References

  1. Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 68(1):7–30. https://doi.org/10.3322/caac.21442

    Article  PubMed  Google Scholar 

  2. American cancer Society (2018) Cancer facts and figs. 2018. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2018/cancer-facts-and-figures-2018.pdf. Accessed 16 Aug 2018

  3. Andre F, Bachelot T, Commo F, Campone M, Arnedos M, Dieras V, Lacroix-Triki M, Lacroix L, Cohen P, Gentien D, Adelaide J, Dalenc F, Goncalves A, Levy C, Ferrero JM, Bonneterre J, Lefeuvre C, Jimenez M, Filleron T, Bonnefoi H (2014) Comparative genomic hybridisation array and DNA sequencing to direct treatment of metastatic breast cancer: a multicentre, prospective trial (SAFIR01/UNICANCER). Lancet Oncol 15(3):267–274. https://doi.org/10.1016/S1470-2045(13)70611-9

    Article  CAS  PubMed  Google Scholar 

  4. Harbeck N, Gnant M (2017) Breast cancer. Lancet 389(10074):1134–1150. https://doi.org/10.1016/S0140-6736(16)31891-8

    Article  PubMed  Google Scholar 

  5. Chia SK, Speers CH, D’Yachkova Y, Kang A, Malfair-Taylor S, Barnett J, Coldman A, Gelmon KA, O’Reilly SE, Olivotto IA (2007) The impact of new chemotherapeutic and hormone agents on survival in a population-based cohort of women with metastatic breast cancer. Cancer 110(5):973–979. https://doi.org/10.1002/cncr.22867

    Article  PubMed  Google Scholar 

  6. Clark GM, Sledge GW Jr, Osborne CK, McGuire WL (1987) Survival from first recurrence: relative importance of prognostic factors in 1,015 breast cancer patients. J Clin Oncol 5(1):55–61

    Article  CAS  PubMed  Google Scholar 

  7. Tevaarwerk AJ, Gray RJ, Schneider BP, Smith ML, Wagner LI, Fetting JH, Davidson N, Goldstein LJ, Miller KD, Sparano JA (2013) Survival in patients with metastatic recurrent breast cancer after adjuvant chemotherapy: little evidence of improvement over the past 30 years. Cancer 119(6):1140–1148. https://doi.org/10.1002/cncr.27819

    Article  PubMed  Google Scholar 

  8. Dawood S, Broglio K, Gonzalez-Angulo AM, Buzdar AU, Hortobagyi GN, Giordano SH (2008) Trends in survival over the past two decades among white and black patients with newly diagnosed stage IV breast cancer. J Clin Oncol 26(30):4891–4898. https://doi.org/10.1200/JCO.2007.14.1168

    Article  PubMed  PubMed Central  Google Scholar 

  9. Largillier R, Ferrero JM, Doyen J, Barriere J, Namer M, Mari V, Courdi A, Hannoun-Levi JM, Ettore F, Birtwisle-Peyrottes I, Balu-Maestro C, Marcy PY, Raoust I, Lallement M, Chamorey E (2008) Prognostic factors in 1,038 women with metastatic breast cancer. Ann Oncol 19(12):2012–2019. https://doi.org/10.1093/annonc/mdn424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Giordano SH, Buzdar AU, Smith TL, Kau SW, Yang Y, Hortobagyi GN (2004) Is breast cancer survival. improving? Cancer 100(1):44–52. https://doi.org/10.1002/cncr.11859

    Article  PubMed  Google Scholar 

  11. Dawood S, Broglio K, Buzdar AU, Hortobagyi GN, Giordano SH (2010) Prognosis of women with metastatic breast cancer by HER2 status and trastuzumab treatment: an institutional-based review. J Clin Oncol 28(1):92–98. https://doi.org/10.1200/JCO.2008.19.9844

    Article  CAS  PubMed  Google Scholar 

  12. Wallwiener M, Riethdorf S, Hartkopf AD, Modugno C, Nees J, Madhavan D, Sprick MR, Schott S, Domschke C, Baccelli I, Schonfisch B, Burwinkel B, Marme F, Heil J, Sohn C, Pantel K, Trumpp A, Schneeweiss A (2014) Serial enumeration of circulating tumor cells predicts treatment response and prognosis in metastatic breast cancer: a prospective study in 393 patients. BMC Cancer 14:512. https://doi.org/10.1186/1471-2407-14-512

    Article  PubMed  PubMed Central  Google Scholar 

  13. de Duenas EM, Hernandez AL, Zotano AG, Carrion RM, Lopez-Muniz JI, Novoa SA, Rodriguez AL, Fidalgo JA, Lozano JF, Gasion OB, Carrascal EC, Capilla AH, Lopez-Barajas IB, Mateu MM, de Ceballos Reyna MH, Ferrando AO, Janez NM, Ballerini VC, Torres AA, Catalan G, Saenz JA, Menjon S, Gonzalez-Angulo AM (2014) Prospective evaluation of the conversion rate in the receptor status between primary breast cancer and metastasis: results from the GEICAM 2009-03 ConvertHER study. Breast Cancer Res Treat 143(3):507–515. https://doi.org/10.1007/s10549-013-2825-2

    Article  PubMed  PubMed Central  Google Scholar 

  14. Sari E, Guler G, Hayran M, Gullu I, Altundag K, Ozisik Y (2011) Comparative study of the immunohistochemical detection of hormone receptor status and HER-2 expression in primary and paired recurrent/metastatic lesions of patients with breast cancer. Med Oncol 28(1):57–63. https://doi.org/10.1007/s12032-010-9418-2

    Article  CAS  PubMed  Google Scholar 

  15. Wallwiener M, Hartkopf AD, Riethdorf S, Nees J, Sprick MR, Schonfisch B, Taran FA, Heil J, Sohn C, Pantel K, Trumpp A, Schneeweiss A (2015) The impact of HER2 phenotype of circulating tumor cells in metastatic breast cancer: a retrospective study in 107 patients. BMC Cancer 15:403. https://doi.org/10.1186/s12885-015-1423-6

    Article  PubMed  PubMed Central  Google Scholar 

  16. Van Poznak C, Somerfield MR, Bast RC, Cristofanilli M, Goetz MP, Gonzalez-Angulo AM, Hicks DG, Hill EG, Liu MC, Lucas W, Mayer IA, Mennel RG, Symmans WF, Hayes DF, Harris LN (2015) Use of biomarkers to guide decisions on systemic therapy for women with metastatic breast cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 33(24):2695–2704. https://doi.org/10.1200/JCO.2015.61.1459

    Article  PubMed  PubMed Central  Google Scholar 

  17. Wallwiener M, Hartkopf AD, Baccelli I, Riethdorf S, Schott S, Pantel K, Marme F, Sohn C, Trumpp A, Rack B, Aktas B, Solomayer EF, Muller V, Janni W, Schneeweiss A, Fehm TN (2013) The prognostic impact of circulating tumor cells in subtypes of metastatic breast cancer. Breast Cancer Res Treat 137(2):503–510. https://doi.org/10.1007/s10549-012-2382-0

    Article  PubMed  Google Scholar 

  18. Pantel K, Speicher MR (2016) The biology of circulating tumor cells. Oncogene 35(10):1216–1224. https://doi.org/10.1038/onc.2015.192

    Article  CAS  PubMed  Google Scholar 

  19. Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P, Varela I, Phillimore B, Begum S, McDonald NQ, Butler A, Jones D, Raine K, Latimer C, Santos CR, Nohadani M, Eklund AC, Spencer-Dene B, Clark G, Pickering L, Stamp G, Gore M, Szallasi Z, Downward J, Futreal PA, Swanton C (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366(10):883–892

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Cristofanilli M (2014) Circulating tumour cells: telling the truth about metastasis. Lancet Oncol 15(4):365–366. https://doi.org/10.1016/S1470-2045(14)70091-9

    Article  PubMed  Google Scholar 

  21. Baccelli I, Schneeweiss A, Riethdorf S, Stenzinger A, Schillert A, Vogel V, Klein C, Saini M, Bauerle T, Wallwiener M, Holland-Letz T, Hofner T, Sprick M, Scharpff M, Marme F, Sinn HP, Pantel K, Weichert W, Trumpp A (2013) Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay. Nat Biotechnol 31(6):539–544. https://doi.org/10.1038/nbt.2576

    Article  CAS  PubMed  Google Scholar 

  22. Bidard FC, Peeters DJ, Fehm T, Nole F, Gisbert-Criado R, Mavroudis D, Grisanti S, Generali D, Garcia-Saenz JA, Stebbing J, Caldas C, Gazzaniga P, Manso L, Zamarchi R, de Lascoiti AF, De Mattos-Arruda L, Ignatiadis M, Lebofsky R, van Laere SJ, Meier-Stiegen F, Sandri MT, Vidal-Martinez J, Politaki E, Consoli F, Bottini A, Diaz-Rubio E, Krell J, Dawson SJ, Raimondi C, Rutten A, Janni W, Munzone E, Caranana V, Agelaki S, Almici C, Dirix L, Solomayer EF, Zorzino L, Johannes H, Reis-Filho JS, Pantel K, Pierga JY, Michiels S (2014) Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data. Lancet Oncol 15(4):406–414. https://doi.org/10.1016/S1470-2045(14)70069-5

    Article  PubMed  Google Scholar 

  23. Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, Reuben JM, Doyle GV, Allard WJ, Terstappen LW, Hayes DF (2004) Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 351(8):781–791. https://doi.org/10.1056/NEJMoa040766

    Article  CAS  PubMed  Google Scholar 

  24. Cristofanilli M, Hayes DF, Budd GT, Ellis MJ, Stopeck A, Reuben JM, Doyle GV, Matera J, Allard WJ, Miller MC, Fritsche HA, Hortobagyi GN, Terstappen LW (2005) Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin Oncol 23(7):1420–1430. https://doi.org/10.1200/JCO.2005.08.140

    Article  PubMed  Google Scholar 

  25. Jansson S, Bendahl PO, Larsson AM, Aaltonen KE, Ryden L (2016) 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 16:433. https://doi.org/10.1186/s12885-016-2406-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Deutsch TM, Riethdorf S, Nees J, Hartkopf AD, Schonfisch B, Domschke C, Sprick MR, Schutz F, Brucker SY, Stefanovic S, Sohn C, Pantel K, Trumpp A, Schneeweiss A, Wallwiener M (2016) Impact of apoptotic circulating tumor cells (aCTC) in metastatic breast cancer. Breast Cancer Res Treat 160(2):277–290. https://doi.org/10.1007/s10549-016-3997-3

    Article  CAS  PubMed  Google Scholar 

  27. Kallergi G, Konstantinidis G, Markomanolaki H, Papadaki MA, Mavroudis D, Stournaras C, Georgoulias V, Agelaki S (2013) Apoptotic circulating tumor cells in early and metastatic breast cancer patients. Mol Cancer Ther 12(9):1886–1895. https://doi.org/10.1158/1535-7163.MCT-12-1167

    Article  CAS  PubMed  Google Scholar 

  28. Madhavan D, Zucknick M, Wallwiener M, Cuk K, Modugno C, Scharpff M, Schott S, Heil J, Turchinovich A, Yang R, Benner A, Riethdorf S, Trumpp A, Sohn C, Pantel K, Schneeweiss A, Burwinkel B (2012) Circulating miRNAs as surrogate markers for circulating tumor cells and prognostic markers in metastatic breast cancer. Clin Cancer Res 18(21):5972–5982. https://doi.org/10.1158/1078-0432.CCR-12-1407

    Article  CAS  PubMed  Google Scholar 

  29. Baccelli I, Stenzinger A, Vogel V, Pfitzner BM, Klein C, Wallwiener M, Scharpff M, Saini M, Holland-Letz T, Sinn HP, Schneeweiss A, Denkert C, Weichert W, Trumpp A (2014) Co-expression of MET and CD47 is a novel prognosticator for survival of luminal breast cancer patients. OncoTarget 5(18):8147–8160. https://doi.org/10.18632/oncotarget.2385

    Article  PubMed  PubMed Central  Google Scholar 

  30. McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM, Statistics Subcommittee of NCIEWGoCD (2006) REporting recommendations for tumor MARKer prognostic studies (REMARK). Breast Cancer Res Treat 100(2):229–235. https://doi.org/10.1007/s10549-006-9242-8

    Article  PubMed  Google Scholar 

  31. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247. https://doi.org/10.1016/j.ejca.2008.10.026

    Article  CAS  PubMed  Google Scholar 

  32. Riethdorf S, Fritsche H, Muller V, Rau T, Schindlbeck C, Rack B, Janni W, Coith C, Beck K, Janicke F, Jackson S, Gornet T, Cristofanilli M, Pantel K (2007) Detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer: a validation study of the CellSearch system. Clin Cancer Res 13(3):920–928. https://doi.org/10.1158/1078-0432.CCR-06-1695

    Article  CAS  PubMed  Google Scholar 

  33. Bidard FC, Proudhon C, Pierga JY (2016) Circulating tumor cells in breast cancer. Mol Oncol 10(3):418–430. https://doi.org/10.1016/j.molonc.2016.01.001

    Article  PubMed  PubMed Central  Google Scholar 

  34. Clark TG, Altman DG, De Stavola BL (2002) Quantification of the completeness of follow-up. Lancet 359(9314):1309–1310

    Article  PubMed  Google Scholar 

  35. von Allmen RS, Weiss S, Tevaearai HT, Kuemmerli C, Tinner C, Carrel TP, Schmidli J, Dick F (2015) Completeness of follow-up determines validity of study findings: results of a prospective repeated measures cohort study. PLoS ONE 10(10):e0140817. https://doi.org/10.1371/journal.pone.0140817

    Article  CAS  Google Scholar 

  36. Liu MC, Shields PG, Warren RD, Cohen P, Wilkinson M, Ottaviano YL, Rao SB, Eng-Wong J, Seillier-Moiseiwitsch F, Noone AM, Isaacs C (2009) Circulating tumor cells: a useful predictor of treatment efficacy in metastatic breast cancer. J Clin Oncol 27(31):5153–5159. https://doi.org/10.1200/JCO.2008.20.6664

    Article  PubMed  PubMed Central  Google Scholar 

  37. Pierga JY, Hajage D, Bachelot T, Delaloge S, Brain E, Campone M, Dieras V, Rolland E, Mignot L, Mathiot C, Bidard FC (2012) 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 23(3):618–624. https://doi.org/10.1093/annonc/mdr263

    Article  PubMed  Google Scholar 

  38. Nole F, Munzone E, Zorzino L, Minchella I, Salvatici M, Botteri E, Medici M, Verri E, Adamoli L, Rotmensz N, Goldhirsch A, Sandri MT (2008) Variation of circulating tumor cell levels during treatment of metastatic breast cancer: prognostic and therapeutic implications. Ann Oncol 19(5):891–897. https://doi.org/10.1093/annonc/mdm558

    Article  CAS  PubMed  Google Scholar 

  39. Budd GT, Cristofanilli M, Ellis MJ, Stopeck A, Borden E, Miller MC, Matera J, Repollet M, Doyle GV, Terstappen LW, Hayes DF (2006) Circulating tumor cells versus imaging—predicting overall survival in metastatic breast cancer. Clin Cancer Res 12(21):6403–6409. https://doi.org/10.1158/1078-0432.CCR-05-1769

    Article  CAS  PubMed  Google Scholar 

  40. Yu M, Bardia A, Wittner BS, Stott SL, Smas ME, Ting DT, Isakoff SJ, Ciciliano JC, Wells MN, Shah AM, Concannon KF, Donaldson MC, Sequist LV, Brachtel E, Sgroi D, Baselga J, Ramaswamy S, Toner M, Haber DA, Maheswaran S (2013) Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science 339(6119):580–584. https://doi.org/10.1126/science.1228522

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Beerling E, Seinstra D, de Wit E, Kester L, van der Velden D, Maynard C, Schafer R, van Diest P, Voest E, van Oudenaarden A, Vrisekoop N, van Rheenen J (2016) Plasticity between epithelial and mesenchymal states unlinks EMT from metastasis-enhancing stem cell capacity. Cell Rep 14(10):2281–2288. https://doi.org/10.1016/j.celrep.2016.02.034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Smerage JB, Barlow WE, Hortobagyi GN, Winer EP, Leyland-Jones B, Srkalovic G, Tejwani S, Schott AF, O’Rourke MA, Lew DL, Doyle GV, Gralow JR, Livingston RB, Hayes DF (2014) Circulating tumor cells and response to chemotherapy in metastatic breast cancer: SWOG S0500. J Clin Oncol 32(31):3483–3489. https://doi.org/10.1200/JCO.2014.56.2561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Rossi G, Mu Z, Rademaker AW, Austin LK, Strickland KS, Costa RLB, Nagy RJ, Zagonel V, Taxter TJ, Behdad A, Wehbe FH, Platanias LC, Gradishar WJ, Cristofanilli M (2018) Cell-free DNA and circulating tumor cells: comprehensive liquid biopsy analysis in advanced breast cancer. Clin Cancer Res 24(3):560–568. https://doi.org/10.1158/1078-0432.CCR-17-2092

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank all the patients who participated in this study. We gratefully acknowledge the medical and nursing staff at the National Center for Tumor Diseases (NCT) Heidelberg and the University Hospital Heidelberg, especially Mirjam Becker, Bettina Mutz, and Martina Scharpff as well as Caroline Modugno for supporting patient recruitment, follow-up, and data collection. We further thank the team involved at University Medical Center Hamburg–Eppendorf for technical assistance during CTC measurement.

Funding

This work was supported by In-house Funds of the National Center for Tumor Diseases (NCT, to AS, no grant number applies). AT has received funding from Swiss Bridge (no grant number applies), the Helmholtz Initiative on Personalized Medicine (iMED, no grant number applies), Europe’s Innovative Medicines Initiative (IMI) Consortium Cancer-ID (115749), the Cancer Core Europe/Transcan Breast Project (01KT1608), the German Federal Ministry of Education and Research (BMBF N02/74829), and the Dietmar Hopp Foundation (no grant number applies).

Author information

Author notes

  1. Markus Wallwiener and Andreas Schneeweiss contributed equally to the study.

Authors and Affiliations

  1. Division of Gynecologic Oncology, National Center for Tumor Diseases (NCT), Heidelberg, Germany

    Sarah F. Jauch, Thomas M. Deutsch, Juliane Nees, Frederik Marmé & Andreas Schneeweiss

  2. Department of Obstetrics and Gynecology, University Hospital Heidelberg, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany

    Sarah F. Jauch, Florian Schütz, Thomas M. Deutsch, Juliane Nees, Barbara Burwinkel, Frederik Marmé, Christof Sohn, Markus Wallwiener & Andreas Schneeweiss

  3. The Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany

    Sarah F. Jauch, Martin R. Sprick, Massimo Saini, Lisa M. Becker & Andreas Trumpp

  4. Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), DKFZ-ZMBH-Alliance, Heidelberg, Germany

    Sarah F. Jauch, Martin R. Sprick, Massimo Saini, Lisa M. Becker & Andreas Trumpp

  5. Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Sabine Riethdorf & Klaus Pantel

  6. Department of Obstetrics and Gynecology, University Hospital Tübingen, Tübingen, Germany

    Birgitt Schönfisch & Sara Y. Brucker

  7. Division of Molecular Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Barbara Burwinkel

  8. Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany

    Peter Sinn

  9. Department of Medical Oncology, National Center for Tumor Diseases (NCT), Heidelberg, Germany

    Dirk Jäger

  10. Faculty of Biosciences, University of Heidelberg, Heidelberg, Germany

    Andreas Trumpp

  11. German Cancer Consortium (DKTK), Heidelberg, Germany

    Andreas Trumpp

Authors
  1. Sarah F. Jauch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sabine Riethdorf
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Martin R. Sprick
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Florian Schütz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Birgitt Schönfisch
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sara Y. Brucker
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Thomas M. Deutsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Juliane Nees
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Massimo Saini
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Lisa M. Becker
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Barbara Burwinkel
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Peter Sinn
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Frederik Marmé
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Klaus Pantel
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Dirk Jäger
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Christof Sohn
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Andreas Trumpp
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Markus Wallwiener
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Andreas Schneeweiss
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sarah F. Jauch.

Ethics declarations

Conflict of interest

FS has served as a Consultant/Advisor for Roche and Novartis and has received Honoraria from Roche, Novartis, and Amgen. FM has served as a Consultant/Advisor for Roche, Pfizer, Novartis, AstraZeneca, and Tesara and has received travel, accommodations, and expenses from Roche, Novartis, Pfizer, AstraZeneca, and Honoraria from Roche, Pfizer, Novartis, Amgen, AstraZeneca, PharmaMar, Genomic Health, and Tesara. MW has provided Expert Testimony for Novartis, has received Honoraria from Novartis and Celgene and travel, accommodations, and expenses from Novartis. AS has received Honoraria from Roche, Celgene, AstraZeneca, Novartis, and Pfizer; research funding from Celgene; and travel, accommodations, and expenses from Roche and Celgene. All remaining authors have declared no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the Ethical Standards of the Institutional and/or National Research Committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jauch, S.F., Riethdorf, S., Sprick, M.R. et al. Sustained prognostic impact of circulating tumor cell status and kinetics upon further progression of metastatic breast cancer. Breast Cancer Res Treat 173, 155–165 (2019). https://doi.org/10.1007/s10549-018-4972-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-018-4972-y

Keywords

Search

Navigation