BACKGROUND:Angiogenesis is involved in all phases of tumor development,and inhibiting angiogenesis may induce a control of tumor growth and metastasis.Anticancer chemotherapy is known to have a direct cytotoxicity effect on tumor cells.However,there are rare reports whether chemotherapy interferes with tumor angiogenesis by influencing the secretion of angiogenic factors from tumor and/or other cells.To address this issue,the changes in circulating VEGF and endostatin (ES) levels during chemotherapy for patients with breast cancer were analyzed and their correlations with tumor angiogenesis and efficacy of chemotherapy were studied.PATIENTS AND METHODS:120 series serum samples were collected form 40 patients with metastatic breast cancer at three times:before chemotherapy and at the end of 1 cycle and 5-6 cycle chemotherapy,and analyzed for VEGF and ES levels using ELISA.Tumor angiogenesis activity was evaluated using the serum soluble vascular cell adhesion molecule (VCAM-1) measured by ELISA as a surrogate marker.RESULTS:(1) Before chemotherapy,median level of VEGF in patients was 496.6pg/ml,and 4.7 times higher than that of controls (P<0.001).Median ES was 95.5ng/ml,and 18.4% lower than that of controls (P=0.183).VCAM-1 was 1077.1ng/ml,and higher than that of controls (P<0.001).Serum VEGF levels correlated with VCAM-1 levels,tumor stage and metastatic site (P<0.05).(2) At the end of 1 cycle chemotherapy,serum VEGF levels (median 524.8pg/ml)were higher compared with pretreatment values (P=0.047),whereas the levels of ES and VCAM-1 were not significantly altered (110.5ng/ml; P=0.055 and 975.6ng/ml; P=0.27).(3)At the end of 5-6 cycles,the change in VEGF level correlated with response to therapy.Serum VEGF levels in 27 patients with responsive and stable disease showed a significant decrease (median 287.4pg/ml),neither but in 13 patients with progressive disease.VCAM1 also showed a treatment-related change like VEGF.However,chemotherapy might only have a minor effect on ES level,because there were not significant differences on the ES levels among 5-6 cycles,1 cycle patients and controls,and neither between different responsive patients.Conclusion:Systemic chemotherapy for breast cancer results in a significant decrease of serum VEGF level,which provides some information about the disease controlled,and tumor angiogenesis switch may trends to an anti-angiogenesis balance following treatmentinduced response or stabilization.The resultant balance may be intensified if chemotherapy combines with antiangiogenesis therapy,which is helpful for accelerating the death of tumor cells and increasing efficacy of chemotherapy.