Incremental increase in VEGFR1 + hematopoietic progenitor cells and VEGFR2 + endothelial progenitor cells predicts relapse and lack of tumor response in breast cancer patients

Sarika Jain, Maureen M. Ward, Jennifer O'Loughlin, Marissa Boeck, Naomi Wiener, Ellen Chuang, Tessa Cigler, Anne Moore, Diana Donovan, Christina Lam, Marta V. Cobham, Sarah Schneider, Paul Christos, Rebecca N. Baergen, Alexander Swistel, Maureen E. Lane, Vivek Mittal, Shahin Rafii, Linda T. Vahdat

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Animal models have demonstrated the critical role of bone marrow-derived VEGFR1 + hematopoietic progenitor cells (HPCs) and VEGFR2 + endothelial progenitor cells (EPCs) in metastatic progression. We explored whether these cells could predict relapse and response in breast cancer (BC) patients. One hundred and thirty-two patients with stages 1-4 BC were enrolled on 2 studies. Circulating CD45 +/CD34 +/VEGFR1 + HPCs and CD45 dim/CD133 +/VEGFR2 + EPCs were assessed from peripheral blood mononuclear cells using flow cytometry. Changes in HPCs and EPCs were analyzed in (1) patients without overt disease that relapsed and (2) metastatic patients according to response by RECIST. At study entry, 102 patients were without evidence of disease and 30 patients had metastatic BC. Seven patients without evidence of BC by exam, labs, and imaging developed recurrence while on study. Median HPC/ml (range) increased from 645.8 (23.5-1,914) to 2,899 (1,176-37,336), P = 0.016, followed by an increase in median EPC/ml from 21.3 (4.7-42.5) to 94.7 (28.2-201.3), P = 0.016, prior to clinical relapse. In metastatic patients with progressive disease, median HPC/ml increased from 1,696 (10-16,470) to 5,124 (374-77,605), P = 0.0009, and median EPC/ml increased from 26 (0-560) to 71 (0-615) prior to progression, P = 0.10. In patients with responding disease, median HPC/ml decreased from 6,147 (912-85,070) to 633 (47-18,065), P = 0.05, and EPC/ml decreased from 46 (0-197) to 23 (0-105), P = 0.41, at response. There were no significant changes in these cells over time in patients with stable disease. Circulating bone marrow-derived HPCs and EPCs predict relapse and disease progression in BC patients.

Original languageEnglish (US)
Pages (from-to)235-242
Number of pages8
JournalBreast Cancer Research and Treatment
Volume132
Issue number1
DOIs
StatePublished - Feb 2012

Keywords

  • Angiogenic switch
  • Breast cancer
  • Metastasis
  • VEGFR1
  • VEGFR2

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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