Purpose
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.
Experimental Design
132 patients with stages 1 to 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.
Results
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 (23.5-1914), 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 1696 (10-16470) to 5124 (374-77605), 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 6147 (912-85070) to 633 (47-18065), 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.
Conclusions
Circulating bone marrow-derived HPCs and EPCs predict relapse and disease progression in BC patients.
Fourteen patients with metastatic breast cancer previously treated with one chemotherapy regimen received Pirarubicin at a dose of 70 mg/m2 at 3-week intervals. In 7 patients the dose had to be reduced, in 1 patient to 40 mg/m2 and in 6 patients to 50–60 mg/m2. There were 1 complete and 2 partial remissions. These objective responses were observed in soft tissue, lung and pleural areas and lasted 1+; 4+ and 5+ months. Grade 3 and 4 leukopenia was found in 42%, grade 3 thrombocytopenia in 2%, grade 3 nausea/vomiting in 29% of the cycles. Grade 1 and 2 alopecia occurred in 64% of the patients, the remaining 36% of the patients did not suffer from any alopecia. No cardiotoxic side effects were observed in 13 patients. In 1 patient with severe coronary heart disease extrasystoles and reduction in left ventricular ejection fraction occurred. Pirarubicin has antitumor activity in previously treated metastatic breast cancer patients.
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