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


Authors: Cristofanilli, M.; Pierga, J. Y.; Reuben, J.; Rademaker, A.; Davis, A. A.; Peeters, D. J.; Fehm, T.; Nolé, F.; Gisbert-Criado, R.; Mavroudis, D.; Grisanti, S.; Giuliano, M.; Garcia-Saenz, J. A.; Stebbing, J.; Caldas, C.; Gazzaniga, P.; Manso, L.; Zamarchi, R.; de Lascoiti, A. F.; De Mattos-Arruda, L.; Ignatiadis, M.; Cabel, L.; van Laere, S. J.; Meier-Stiegen, F.; Sandri, M. T.; Vidal-Martinez, J.; Politaki, E.; Consoli, F.; Generali, D.; Cappelletti, M. R.; Diaz-Rubio, E.; Krell, J.; Dawson, S. J.; Raimondi, C.; Rutten, A.; Janni, W.; Munzone, E.; Carañana, V.; Agelaki, S.; Almici, C.; Dirix, L.; Solomayer, E. F.; Zorzino, L.; Darrigues, L.; Reis-Filho, J. S.; Gerratana, L.; Michiels, S.; Bidard, F. C.; Pantel, K.
Review Title: The clinical use of circulating tumor cells (CTCs) enumeration for staging of metastatic breast cancer (MBC): International expert consensus paper
Abstract: 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 IVaggressive, those with < 5 CTCs as Stage IVindolent. Survival was analyzed using Kaplan-Meier curves and the log rank test. Results: For all patients, Stage IVindolent patients had longer median overall survival than those with Stage IVaggressive (36.3 months vs. 16.0 months, P < 0.0001) and similarly for de novo MBC patients (41.4 months Stage IVindolent vs. 18.7 months Stage IVaggressive, p < 0.0001). Moreover, patients with Stage IVindolent 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 IVindolent and Stage IVaggressive, 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
Keywords: survival; adult; cancer survival; controlled study; aged; survival analysis; major clinical study; overall survival; review; cancer localization; cancer staging; outcome assessment; cohort analysis; retrospective study; biomarker; metastatic breast cancer; circulating tumor cells; circulating tumor cell; triple negative breast cancer; cancer prognosis; human epidermal growth factor receptor 2 positive breast cancer; human; female; cell counting; ctcs; mbc
Journal Title: Critical Reviews in Oncology/Hematology
Volume: 134
ISSN: 1040-8428
Publisher: Elsevier Science, Inc.  
Date Published: 2019-02-01
Start Page: 39
End Page: 45
Language: English
DOI: 10.1016/j.critrevonc.2018.12.004
PROVIDER: scopus
PUBMED: 30771872
DOI/URL:
Notes: Review -- Export Date: 1 February 2019 -- Source: Scopus
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