Circulating small-sized endothelial microparticles as predictors of clinical outcome after chemotherapy for breast cancer: an exploratory analysis
Therapeutic exploitation of angiogenesis in breast cancer has been limited by the lack of reliable biomarkers. Circulating small-sized endothelial microparticles (sEMP) are likely to play a significant role as messengers of angiogenesis. Higher levels of EMP have been observed in cancer patients, but their prognostic value in breast cancer is unknown. Our aim was to determine the value of circulating sEMP as a marker of response to chemotherapy in breast cancer.
We included patients with breast cancer treated with neoadjuvant or first-line chemotherapy. Baseline and post-treatment circulating sEMP (CD144+) were quantified using a flow cytometer approach specifically designed for analysis of small-sized particles (0.1–0.5 μm). Small-sized EMP response was defined as a post-treatment decrease of sEMP larger than the median decrease of sEMP after chemotherapy. Baseline and post-chemotherapy VEGFA levels were determined with ELISA.
Forty-four breast cancer patients were included (19 with metastatic and 25 with locally advanced disease). Median levels of sEMP decreased after chemotherapy (P = 0.005). Response to chemotherapy showed a non-significant trend to associate with sEMP response (P = 0.056). A sEMP response was observed in 51% of patients and was associated with better overall survival (HR 0.18; 95% CI 0.04–0.87; P = 0.02) and progression free survival (HR 0.30; 95% CI 0.09–0.99; P = 0.04) in the group of women with metastatic disease. Post-chemotherapy decrease of VEGFA levels was not associated with breast cancer prognosis.
Our results did not support sEMP as a marker of response to chemotherapy. However, our exploratory analysis suggests that in patients with metastatic breast cancer, the decrease of sEMP levels after chemotherapy is associated with better overall and disease free survival and might be superior to VEGFA levels as an angiogenesis-related prognostic marker.
KeywordsSmall-sized microparticles Endothelial Breast cancer Chemotherapy VEGFA
Locally advanced breast cancer
Metastatic breast cancer
Small-sized endothelial microparticles
Triple negative breast cancer
Vascular and endothelial growth factor A
We acknowledge technical assistance by José A. López Oliva (Clinical Research Unit, Department of Hematology and Medical Oncology, Hospital Universitario Morales Meseguer) and Alberto Martínez (Biobancmur, Nodo 3, Hospital Universitario Morales Meseguer, IMIB Arrixaca). This work was partially funded by “Calasparra se mueve,” a research-funding initiative inspired by women from Calasparra (Murcia), Spain. SMG was supported by the People Program (Marie Curie Actions) of the European Union’s Seventh Framework Program (FP7/2007-2013) under REA Grant Agreement No. 608765.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in this study were in accordance with the ethical standards of the institution and with the 1964 Helsinki declaration and its later amendments.
Informed consent was obtained from all individual participants included in the study and the Institutional Review Board of Hospital Morales Meseguer approved the study.