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 CD45dim/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.
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Acknowledgments
We greatly appreciate the generous support from the following: Anne Moore Breast Cancer Research Fund, Stephen and Madeline Anbinder Foundation, Rozaliya Kosmandel Research Fund, Susan G Komen for the Cure, New York Community Trust, and Cancer Research and Treatment Fund. We would also like to thank the Weill Cornell Translational Core Laboratory, Rakhi Naik, MD for her initial contribution to the design of Study 1, and Dingchen Gao and Raul Catena for their valuable comments on this manuscript. Dr. Paul Christos was partially supported by the following grant: Clinical Translational Science Center (CTSC) (UL1-RR024996).
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Jain, S., Ward, M.M., O’Loughlin, J. et al. Incremental increase in VEGFR1+ hematopoietic progenitor cells and VEGFR2+ endothelial progenitor cells predicts relapse and lack of tumor response in breast cancer patients. Breast Cancer Res Treat 132, 235–242 (2012). https://doi.org/10.1007/s10549-011-1906-3
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DOI: https://doi.org/10.1007/s10549-011-1906-3