We have identified the baseline VEGF/sVEGFR-2 and VEGF/TSP-1 ratios as potential biomarkers of response in ABCP treated metronomically with Cy+Cel. This finding warrants its confirmation in a higher number of patients.

Our secondary objective was to note the survival according to lymph node biopsy results.

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Low-dose metronomic chemotherapy (MC) with Cyclophosphamide (Cy) and Celecoxib (Cel) has demonstrated to be effective and well-tolerated in advanced breast cancer patients (ABCP) but predictive markers of response or follow-up are lacking. Given the antiangiogenic properties of MC we analyzed several angiogenesis-related biomarkers and evaluated their potential role as predictors of response or treatment follow-up of ABCP treated with MC. Treatment plan: Patients received Cy 50 mg p.o./day + Cel 200 mg p.o./ bid. Cellular parameters: Circulating endothelial cells (CEC) and Circulating progenitor endothelial Cells (CEP) were determined by Flow Cytometry. Serologic parameters: Serum levels of vascular endothelial growth factor (VEGF), VEGF-C, soluble VEGF Receptors 2 and 3 (sVEGFR-2, sVEGFR-3) and Thrombospondin-1 (TSP-1) were determined by ELISA. Blood samples were collected before and during treatment. Twenty patients were enrolled. Response Rate was 5% and Clinical Benefit (CB) 55%. Most of the patients showed prolonged stable disease (SD≥24 weeks). Biomarkers were determined in all patients. Levels of CEC and CEP showed no clear trend variations during treatment. However, levels of CEC significantly increased at the time of disease progression in those patients who showed CB (P=0.014). Also baseline values of CEC and CEP showed marginally significant associations withTime To Progression. Serum VEGF concentration decreased during treatment (P=0.050) while sVEGFR-2 increased (P=0.005). VEGF-C, sVEGFR-3 and TSP-1 showed non-significant variations. VEGF/sVEGFR-2 ratio decreased during treatment (P=0.041), whereas VEGF/TSP-1, and VEGF-C/sVEGFR-2 ratios showed non-significant variations. Baseline values of VEGF, and VEGF/sVEGFR-2 showed negative and significant associations with TTP (P=0.0354 and P=0.0300, respectively) while sVEGFR-2 did not. When considering the two variables together, the goodness of prediction was not improved. To confirm the value of baseline VEGF and VEGF/sVEGFR-2 as predictors of response, we used the 50th percentile as a cutoff value to analyze the % of progression free survival. Patients with values lower than the 50th percentile for both biomarkers showed longer TTP (P=0.0001 and P=0.0008, respectively). The treatment had anti-angiogenic effect (VEGF decrease and sVEGFR-2 increase). The absence of variation in VEGF-C and sVEGFR-3 would indicate the lack of effect on lymphangiogenesis. Increased levels of CEC could be useful for detecting progression. If confirmed with a higher number of patients, baseline VEGF and VEGF/sVEGFR-2 values could be useful as early predictors of response. Citation Format: Perroud HA, Alasino CM, Rico MJ, Menacho-Marquez MA, Mainetti LE, Queralt F, Pezzotto SM, Rozados VR, Scharovsky G. Predictors of response and follow up biomarkers for metronomic chemotherapy with cyclophosphamide and celecoxib in advanced breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-61.