title: Incremental increase in VEGFR1⁺ hematopoietic progenitor cells and VEGFR2⁺ endothelial progenitor cells predicts relapse and lack of tumor response in breast cancer patients.
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.
authors.affiliation: Department of Medicine, Weill Cornell Medical College, Iris Cantor Breast Center, 425 East 61 St, 8th floor, New York, NY 10065, USA.
authors.forename: Sarika
authors.initials: S
authors.lastname: Jain
authors.forename: Maureen M
authors.initials: MM
authors.lastname: Ward
authors.forename: Jennifer
authors.initials: J
authors.lastname: O'Loughlin
authors.forename: Marissa
authors.initials: M
authors.lastname: Boeck
authors.forename: Naomi
authors.initials: N
authors.lastname: Wiener
authors.forename: Ellen
authors.initials: E
authors.lastname: Chuang
authors.forename: Tessa
authors.initials: T
authors.lastname: Cigler
authors.forename: Anne
authors.initials: A
authors.lastname: Moore
authors.forename: Diana
authors.initials: D
authors.lastname: Donovan
authors.forename: Christina
authors.initials: C
authors.lastname: Lam
authors.forename: Marta V
authors.initials: MV
authors.lastname: Cobham
authors.forename: Sarah
authors.initials: S
authors.lastname: Schneider
authors.forename: Paul
authors.initials: P
authors.lastname: Christos
authors.forename: Rebecca N
authors.initials: RN
authors.lastname: Baergen
authors.forename: Alexander
authors.initials: A
authors.lastname: Swistel
authors.forename: Maureen E
authors.initials: ME
authors.lastname: Lane
authors.forename: Vivek
authors.initials: V
authors.lastname: Mittal
authors.forename: Shahin
authors.initials: S
authors.lastname: Rafii
authors.forename: Linda T
authors.initials: LT
authors.lastname: Vahdat
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D002452:Cell Count; D015331:Cohort Studies; D000069439:Dasatinib; D005260:Female; D055018:Hemangioblasts / Q000187:drug effects / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D000077341:Lapatinib; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011743:Pyrimidines / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D013844:Thiazoles / Q000008:administration & dosage; D000068878:Trastuzumab; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D011743:Pyrimidines; D011799:Quinazolines; D013844:Thiazoles; D000077341:Lapatinib; D000068258:Bevacizumab; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D000068878:Trastuzumab; D000069439:Dasatinib