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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)

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Abstract

Background

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).

Methods

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).

Results

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.

Conclusion

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.

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Acknowledgement

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

Author information

Author notes

  1. Antoine Vasseur and Luc Cabel have contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Oncology, Institut Curie, PSL Research University, 26 rue d’Ulm, 75005, Paris & Saint Cloud, France

    Antoine Vasseur, Luc Cabel, Coraline Dubot, Francois-Clement Bidard & Jean-Yves Pierga

  2. UVSQ, Paris-Saclay University, Saint Cloud, France

    Luc Cabel & Francois-Clement Bidard

  3. Department of Medical Oncology, Leon Berard Center, Lyon, France

    Olivier Tredan

  4. Department of Medical Oncology, Georges-François Leclerc Center, Dijon, France

    Véronique Lorgis

  5. Department of Medical Oncology, Institut du Cancer de Montpellier (ICM) Val d’Aurelle, Montpellier University, IRCM INSERM U1194, Montpellier, France

    William Jacot

  6. Aix-Marseille Univ, Inserm U1068, CNRS UMR7258, Institut Paoli-Calmettes, Department of Medical Oncology, CRCM, Marseille, France

    Anthony Goncalves

  7. Department of Medical Oncology, Institut Bergonie, Bordeaux, France

    Marc Debled

  8. Department of Medical Oncology, François Baclesse Center, Caen, France

    Christelle Levy

  9. Department of Medical Oncology, Antoine Lacassagne Center, Nice, France

    Jean-Marc Ferrero

  10. Department of Medical Oncology, Institut Jean Godinot, Reims, France

    Christelle Jouannaud

  11. Department of Medical Oncology, ICL Alexis Vautrin, Vandoeuvre Les Nancy, France

    Elisabeth Luporsi

  12. Department of Medical Oncology, Jean Perrin Center, Clermont-Ferrand, France

    Marie-Ange Mouret-Reynier

  13. Department of Medical Oncology, Institut Claudius Regaud, IUCT-Oncopole, Toulouse, France

    Florence Dalenc

  14. R&D UNICANCER, UCBG, Paris, France

    Jerome Lemonnier

  15. Department of Biostatistics, Institut Curie, PSL Research University, Paris & Saint Cloud, France

    Marion Chevrier, Alexia Savignoni & Marie-Laure Tanguy

  16. Paris Descartes University, Paris, France

    Jean-Yves Pierga

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  1. Antoine Vasseur
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Corresponding author

Correspondence to Jean-Yves Pierga.

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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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Vasseur, A., Cabel, L., Tredan, O. et al. Prognostic value of CEC count in HER2-negative metastatic breast cancer patients treated with bevacizumab and chemotherapy: a prospective validation study (UCBG COMET). Angiogenesis 23, 193–202 (2020). https://doi.org/10.1007/s10456-019-09697-7

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