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Incremental increase in VEGFR1⁺ hematopoietic progenitor cells and VEGFR2⁺ endothelial progenitor cells predicts relapse and lack of tumor response in breast cancer patients.
- Source :
-
Breast cancer research and treatment [Breast Cancer Res Treat] 2012 Feb; Vol. 132 (1), pp. 235-42. Date of Electronic Publication: 2011 Dec 09. - Publication Year :
- 2012
-
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.
- Subjects :
- Adult
Aged
Antibodies, Monoclonal, Humanized administration & dosage
Bevacizumab
Biomarkers, Tumor blood
Biomarkers, Tumor metabolism
Breast Neoplasms blood
Cell Count
Cohort Studies
Dasatinib
Female
Hemangioblasts drug effects
Hematopoietic Stem Cells drug effects
Humans
Lapatinib
Middle Aged
Neoplasm Recurrence, Local
Neoplasm Staging
Pyrimidines administration & dosage
Quinazolines administration & dosage
Thiazoles administration & dosage
Trastuzumab
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Breast Neoplasms drug therapy
Breast Neoplasms pathology
Hemangioblasts metabolism
Hematopoietic Stem Cells metabolism
Vascular Endothelial Growth Factor Receptor-1 metabolism
Vascular Endothelial Growth Factor Receptor-2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1573-7217
- Volume :
- 132
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Breast cancer research and treatment
- Publication Type :
- Academic Journal
- Accession number :
- 22160642
- Full Text :
- https://doi.org/10.1007/s10549-011-1906-3