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Prognostic value of CEC count in HER2-negative metastatic breast cancer patients treated with bevacizumab and chemotherapy: a prospective validation study (UCBG COMET)

  • Antoine Vasseur
  • Luc Cabel
  • Olivier Tredan
  • Marion Chevrier
  • Coraline Dubot
  • Véronique Lorgis
  • William Jacot
  • Anthony Goncalves
  • Marc Debled
  • Christelle Levy
  • Jean-Marc Ferrero
  • Christelle Jouannaud
  • Elisabeth Luporsi
  • Marie-Ange Mouret-Reynier
  • Florence Dalenc
  • Jerome Lemonnier
  • Alexia Savignoni
  • Marie-Laure Tanguy
  • Francois-Clement Bidard
  • Jean-Yves PiergaEmail author
Original Paper



Proof of concept studies has reported that circulating endothelial cell (CEC) count may be associated with the outcome of HER2-negative metastatic breast cancer (mBC) patients treated by chemotherapy and the anti-VEGF antibody bevacizumab. We report the results obtained in an independent prospective validation cohort (COMET study, NCT01745757).


The main baseline criteria were HER2-negative mBC, performance status 0–2 and no prior chemotherapy for metastatic disease. CECs were detected by CellSearch® from 4 ml of blood at baseline and after 4 weeks of weekly paclitaxel and bevacizumab therapy. CEC counts (considered both as a continuous variable and using the previously described 20 CEC/4 ml cutoff) were associated with clinical characteristics and progression-free survival (PFS).


CEC count was obtained in 251 patients at baseline and in 207 patients at 4 weeks. Median baseline CEC count was 22 CEC/4 ml (range 0–2231). Baseline CEC counts were associated with performance status (p = 0.02). No statistically significant change in CEC counts was observed between baseline and 4 weeks of therapy. High baseline CEC count was associated with shorter PFS in univariate and multivariate analyses (continuous: p < 0.001; dichotomized: HR 1.52, 95% CI [1.15–2.02], p = 0.004). CEC counts at 4 weeks had no prognostic impact.


This study confirms that CEC count may be associated with the outcome of mBC patients treated with chemotherapy and bevacizumab. However, discrepancies with previous reports in terms of both the timing of CEC count and the direction of the prognostic impact warrant further clinical investigation.


Bevacizumab Breast cancer Circulating endothelial cells 



We are grateful to patients who participated in the study. This research was funded by Roche. UNICANCER is the sponsor of the study.

Compliance with ethical standards

Conflict of interest

JY Pierga received lecture honoraria, travel grant and research funding from Roche; FC Bidard received travel grant and research funding from Roche, Menarini Silicon Biosystems; A Goncalves received travel, accommodation and meeting registration support from Pfizer, Novartis, Roche, AstraZeneca, MSD, Celgene; O Tredan received honoraria from Roche, Novartis, AstraZeneca, Pfizer, Lilly and MSD for boards and symposiums. Other authors have stated explicitly that they have no conflicts of interest in connection with this article.


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Antoine Vasseur
    • 1
  • Luc Cabel
    • 1
    • 2
  • Olivier Tredan
    • 3
  • Marion Chevrier
    • 15
  • Coraline Dubot
    • 1
  • Véronique Lorgis
    • 4
  • William Jacot
    • 5
  • Anthony Goncalves
    • 6
  • Marc Debled
    • 7
  • Christelle Levy
    • 8
  • Jean-Marc Ferrero
    • 9
  • Christelle Jouannaud
    • 10
  • Elisabeth Luporsi
    • 11
  • Marie-Ange Mouret-Reynier
    • 12
  • Florence Dalenc
    • 13
  • Jerome Lemonnier
    • 14
  • Alexia Savignoni
    • 15
  • Marie-Laure Tanguy
    • 15
  • Francois-Clement Bidard
    • 1
    • 2
  • Jean-Yves Pierga
    • 1
    • 16
    Email author
  1. 1.Department of Medical Oncology, Institut CuriePSL Research UniversityParis & Saint CloudFrance
  2. 2.UVSQ, Paris-Saclay UniversitySaint CloudFrance
  3. 3.Department of Medical OncologyLeon Berard CenterLyonFrance
  4. 4.Department of Medical OncologyGeorges-François Leclerc CenterDijonFrance
  5. 5.Department of Medical Oncology, Institut du Cancer de Montpellier (ICM) Val d’AurelleMontpellier University, IRCM INSERM U1194MontpellierFrance
  6. 6.Aix-Marseille Univ, Inserm U1068, CNRS UMR7258, Institut Paoli-Calmettes, Department of Medical Oncology, CRCMMarseilleFrance
  7. 7.Department of Medical Oncology, Institut BergonieBordeauxFrance
  8. 8.Department of Medical Oncology, François Baclesse CenterCaenFrance
  9. 9.Department of Medical Oncology, Antoine Lacassagne CenterNiceFrance
  10. 10.Department of Medical Oncology, Institut Jean GodinotReimsFrance
  11. 11.Department of Medical OncologyICL Alexis VautrinVandoeuvre Les NancyFrance
  12. 12.Department of Medical Oncology, Jean Perrin CenterClermont-FerrandFrance
  13. 13.Department of Medical Oncology, Institut Claudius Regaud, IUCT-OncopoleToulouseFrance
  14. 14.R&D UNICANCER, UCBGParisFrance
  15. 15.Department of Biostatistics, Institut CuriePSL Research UniversityParis & Saint CloudFrance
  16. 16.Paris Descartes UniversityParisFrance

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