The clinical use of circulating tumor cells (CTCs) enumeration for staging of metastatic breast cancer (MBC): International expert consensus paper

Massimo Cristofanilli, Jean Yves Pierga, James Reuben, Alfred Rademaker, Andrew A. Davis, Dieter J. Peeters, Tanja Fehm, Franco Nolé, Rafael Gisbert-Criado, Dimitrios Mavroudis, Salvatore Grisanti, Mario Giuliano, Jose A. Garcia-Saenz, Justin Stebbing, Carlos Caldas, Paola Gazzaniga, Luis Manso, Rita Zamarchi, Angela Fernandez de Lascoiti, Leticia De Mattos-ArrudaMichail Ignatiadis, Luc Cabel, Steven J. van Laere, Franziska Meier-Stiegen, Maria Teresa Sandri, Jose Vidal-Martinez, Eleni Politaki, Francesca Consoli, Daniele Generali, Maria Rosa Cappelletti, Eduardo Diaz-Rubio, Jonathan Krell, Sarah Jane Dawson, Cristina Raimondi, Annemie Rutten, Wolfgang Janni, Elisabetta Munzone, Vicente Carañana, Sofia Agelaki, Camillo Almici, Luc Dirix, Erich Franz Solomayer, Laura Zorzino, Lauren Darrigues, Jorge S. Reis-Filho, Lorenzo Gerratana, Stefan Michiels, François Clément Bidard, Klaus Pantel

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186 Scopus citations


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.

Original languageEnglish
Pages (from-to)39-45
Number of pages7
JournalCritical Reviews in Oncology/Hematology
StatePublished - Feb 2019


  • Biomarker
  • CTCs
  • Circulating tumor cells
  • MBC
  • Metastatic breast cancer
  • Survival


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