The clinical use of circulating tumor cells (CTCs) enumeration for staging of metastatic breast cancer (MBC): International expert consensus paper: Critical Reviews in Oncology/Hematology

M. Cristofanilli, J.-Y. Pierga, J. Reuben, A. Rademaker, A.A. Davis, D.J. Peeters, T. Fehm, F. Nolé, R. Gisbert-Criado, D. Mavroudis, S. Grisanti, M. Giuliano, J.A. Garcia-Saenz, J. Stebbing, C. Caldas, P. Gazzaniga, L. Manso, R. Zamarchi, A.F. de Lascoiti, L. De Mattos-ArrudaM. Ignatiadis, L. Cabel, S.J. van Laere, F. Meier-Stiegen, M.-T. Sandri, J. Vidal-Martinez, E. Politaki, F. Consoli, D. Generali, M.R. Cappelletti, E. Diaz-Rubio, J. Krell, S.-J. Dawson, C. Raimondi, A. Rutten, W. Janni, E. Munzone, V. Carañana, S. Agelaki, C. Almici, L. Dirix, E.-F. Solomayer, L. Zorzino, L. Darrigues, J.S. Reis-Filho, L. Gerratana, S. Michiels, F.-C. Bidard, K. Pantel

Research output: Contribution to journalArticlepeer-review


Background: The heterogeneity of metastatic breast cancer (MBC) necessitates novel biomarkers allowing stratification of patients for treatment selection and drug development. We propose to use the prognostic utility of circulating tumor cells (CTCs) for stratification of patients with stage IV disease. Methods: In a retrospective, pooled analysis of individual patient data from 18 cohorts, including 2436 MBC patients, a CTC threshold of 5 cells per 7.5 ml was used for stratification based on molecular subtypes, disease location, and prior treatments. Patients with ≥ 5 CTCs were classified as Stage IV aggressive , those with < 5 CTCs as Stage IV indolent. Survival was analyzed using Kaplan-Meier curves and the log rank test. Results: For all patients, Stage IV indolent patients had longer median overall survival than those with Stage IV aggressive (36.3 months vs. 16.0 months, P < 0.0001) and similarly for de novo MBC patients (41.4 months Stage IV indolent vs. 18.7 months Stage IV aggressive , p < 0.0001). Moreover, patients with Stage IV indolent disease had significantly longer overall survival across all disease subtypes compared to the aggressive cohort: hormone receptor-positive (44 months vs. 17.3 months, P < 0.0001), HER2-positive (36.7 months vs. 20.4 months, P < 0.0001), and triple negative (23.8 months vs. 9.0 months, P < 0.0001). Similar results were obtained regardless of prior treatment or disease location. Conclusions: We confirm the identification of two subgroups of MBC, Stage IV indolent and Stage IV aggressive , independent of clinical and molecular variables. Thus, CTC count should be considered an important tool for staging of advanced disease and for disease stratification in prospective clinical trials. © 2018
Original languageEnglish
Pages (from-to)39-45
Number of pages7
JournalCrit. Rev. Oncol. Hematol.
Publication statusPublished - 2019


  • Biomarker
  • Circulating tumor cells
  • CTCs
  • MBC
  • Metastatic breast cancer
  • Survival
  • adult
  • aged
  • cancer localization
  • cancer prognosis
  • cancer staging
  • cancer survival
  • cell counting
  • circulating tumor cell
  • cohort analysis
  • controlled study
  • female
  • human
  • human epidermal growth factor receptor 2 positive breast cancer
  • major clinical study
  • metastatic breast cancer
  • outcome assessment
  • overall survival
  • retrospective study
  • Review
  • survival analysis
  • triple negative breast cancer
  • breast tumor
  • consensus
  • expert witness
  • international cooperation
  • pathology
  • patient selection
  • standards
  • tumor embolism
  • tumor marker
  • Biomarkers, Tumor
  • Breast Neoplasms
  • Consensus
  • Expert Testimony
  • Female
  • Humans
  • International Agencies
  • Neoplasm Staging
  • Neoplastic Cells, Circulating
  • Patient Selection


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