Low Pre-Treatment Count of Circulating Endothelial Progenitors as a Prognostic Biomarker of the High Risk of Breast Cancer Recurrence

Abstract

Neoangiogenesis is mediated by circulating bone marrow-derived endothelial progenitors (circulating EPCs). The aim of the study was the quantification of circulating EPCs from the peripheral blood mononuclear cells of invasive breast cancer (IBrC) patients by flow cytometry, before and after cancer adjuvant treatment. A total of 88 stage IA-IIB primary IBrC patients were enrolled prospectively. Circulating EPCs with the immune-phenotype CD45−CD34+CD133+CD31+ were assessed. Treatment significantly reduced the number of EPCs/µL in the general IBrC cohort. However, there was a relevant elevation in the number of circulating EPCs after nine months of adjuvant treatment in the group of patients aged ≥ 55 years, of T2 clinical type, with nodal involvement (N1) and Ki67 expression > 15%. Follow-up revealed a significantly higher incidence of disease relapse in breast cancer patients with low pre-treatment circulating EPCs levels compared with those with a high baseline circulating EPCs count. The receiver-operating characteristic curve identified a tumour diameter of 2.1 cm as the best cut-off value to discriminate between disease-relapse subjects and non-relapse disease cases. Our study strongly indicates that, next to tumour diameter and Ki67 expression, circulating bone marrow-derived EPCs may serve as useful markers for predicting therapeutic outcomes as well as a future prognosis.

Stromal Cell-Derived Factor 1α (SDF-1α) in Invasive Breast Cancer: Associations with Vasculo-Angiogenic Factors and Prognostic Significance

“…The number of circulating EPCs was determined using a method and recommendations provided by Mancuso et al and our previous study [ 15 , 16 ]. Pre-treatment blood samples collected with EDTA were analysed on the FACSCaliburTM (BD Bioscience, San Jose, CA, USA) for four-color immunophenotyping.…”

“…Circulating EPCs were thus defined according to the following immunophenotype: CD45−CD34+CD133+CD31+. The laboratory procedure is described in our former paper [ 16 ].…”

“…Oestrogen receptor expression (ER) and progesterone receptor expression (PR) were expressed as positive or negative. The ER and PR variables were then categorised into combined hormone receptor expression (ER+PR+ or ER+PR-/ER-PR+/ER-PR-), as previously published [ 16 ].…”

Divergent Impact of Breast Cancer Laterality on Clinicopathological, Angiogenic, and Hemostatic Profiles: A Potential Role of Tumor Localization in Future Outcomes

“…According to the World Health Organization definition, patients were classified into three BMI subgroups: normal weight (18.5 to 24.9 kg/m 2 ), overweight (25.0 to 29.9 kg/m 2 ), obese (>30.0 kg/m 2 ). Full details of the study recruitment and procedures were previously reported [ 12 ].…”

“…These included the administration of adjuvant chemotherapy, immunotherapy, hormonal therapy, or a combination, as well as radiation therapy details including primary target (breast vs. breast and regional nodes, use of boost, and prescribed dose). None of the patients were taking any drugs with hemostatic and fibrinolytic effects [ 12 ].…”