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

Angiogenesis. 2020 May;23(2):193-202. doi: 10.1007/s10456-019-09697-7. Epub 2019 Nov 26.

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.

Keywords: Bevacizumab; Breast cancer; Circulating endothelial cells.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab / administration & dosage*
  • Biomarkers, Pharmacological / analysis
  • Biomarkers, Tumor / analysis
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Breast Neoplasms, Male / diagnosis
  • Breast Neoplasms, Male / drug therapy
  • Breast Neoplasms, Male / genetics
  • Breast Neoplasms, Male / pathology
  • Cell Count
  • Endothelial Cells / drug effects
  • Endothelial Cells / pathology*
  • Female
  • Genes, erbB-2
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplastic Cells, Circulating / drug effects
  • Neoplastic Cells, Circulating / pathology*
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies

Substances

  • Biomarkers, Pharmacological
  • Biomarkers, Tumor
  • Bevacizumab

Associated data

  • ClinicalTrials.gov/NCT01745757