Circulating levels of angiogenic cytokines in advanced breast cancer patients with system chemotherapy and their potential value in monitoring disease course.

PURPOSE: The low-dose metronomic chemotherapy was reported to inhibit directly tumor angiogenesis or VEGF secretion. The study aimed to seek for this effect of system chemotherapy by observing the changes in serum levels of angiogenic cytokines during treatment and assessing their value in monitoring the advanced breast cancer. METHODS: In sixty-one patients with advanced breast cancer, serum levels of vascular endothelial growth factor (VEGF) and endostatin (ES) were compared at baseline (B0), after one cycle (B1), after 3 cycles (B3), and after 5-6 cycles (B5-6) of system chemotherapy using a quantitative ELISA. Data were correlated with treatment response and total survival. RESULTS: The response to chemotherapy did not correlate with serum VEGF level before therapy or after one cycle, but the changes in VEGF levels after 3 cycles and 5-6 cycles showed good association with clinical responses, i.e., the patients with disease control had a decreased VEGF value, whereas the progressive patients had an increased value. The Cox proportional hazard model revealed that a normalized VEGF level after therapy and an increase in VEGF level after 5-6 cycles were independent predictors for survival. CONCLUSIONS: System chemotherapy for advanced breast cancer lead to a significant decrease in serum VEGF level in patients with disease control, and this anti-VEGF efficacy may be mainly due to the reduction in tumor burden. Sequential measurement of serum VEGF could be useful for evaluating treatment efficacy and prognosis.