Abstract 3740: Circulating endothelial progenitor cells as a predictive biomarker of acute skin toxicity in early breast cancer patients undergoing radiation therapy

Abstract

Abstract Background/Purpose: Acute skin toxicity is a common side effect of radiation therapy (RT) in breast-cancer patients. We hypothesized that RT modulates the levels of circulating endothelial cells with a progenitor-like phenotype (EPCs) and/or circulating endothelial cells (CECs), which in turn may affect the repair of radiation injury. So far, the association between the mobilization of EPCs, the levels of CECs and RT-induced skin toxicity has not been investigated in breast cancer patients. We assessed whether RT increased the levels of EPCs and/or CECs and whether this increase may predict RT-induced skin toxicity in early breast cancer patients undergoing RT in a prospective clinical study. Patients/Methods: Sixty-five early breast cancer patients were treated with adjuvant RT after lumpectomy. The dose delivered to the entire breast was 50 Gy in 25 fractions over 5 weeks. Patients were evaluated weekly for acute skin toxicity using the National Cancer Institute's Common Toxicity Criteria, version 3.0. EPCs (CD45dim, CD31+ and CD133+), CECs (CD45-, CD31+ and CD146+), and vascular endothelial growth factor receptor 2 (VEGFR-2)-positive cells (CD45dim, CD31+ and VEGFR-2+) were enumerated from blood samples by multicolor flow cytometry before RT (T1) and 24h post-RT (T3). Total RNA was extracted from blood samples and the levels of CD133, CD146 and VEGFR-2 were determined using quantitative real-time reverse transcription polymerase chain reaction (Q-RT-PCR). Results: Flow cytometry analysis revealed that RT within 24h significantly increased EPCs (CD45dim, CD31+ and CD133+, p = 0.0027), (CD45dim, CD31+, VEGFR-2+, p = 0.0020)-positive cells, but not CECs (CD45-, CD31+ and CD146+, p = 0.8415) using Chi-square test. Increased EPCs was highly correlated to the increase of (CD45dim, CD31+, VEGFR-2+)-positive cells using Pearson correlation coefficient (p = 0.0118). Accordingly, as assessed by Q-RT-PCR, expression of CD133 and VEGFR-2, but not CD146 was significantly increased (p = 0.0027; p = 0.1615; p = 0.5485, using normalized gene expression values). Univariate analysis showed that increased CD133 or VEGFR-2 levels, 24h following RT was significantly correlated with acute toxicity (logrank p-value 0.0163; 0.0025, respectively). Conclusions: Our preliminary results suggest that focal RT is able to induce a systemic response, which promotes rapid mobilization of bone marrow-derived cells EPCs (within 24h), and does not significantly affect the levels of CECs. Furthermore, quantitative analysis of EPCs levels by flow cytometry or Q-RT-PCR correlates with increased acute skin toxicity. Our findings suggest for the first time that mobilization of EPCs following RT could be proposed as an early surrogate biomarker for acute skin toxicity in breast cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3740.