Objective: To study the changes in circulating VEGF and endostatin (ES) levels during chemotherapy for patients with breast cancer, and their correlation with efficacy of chemotherapy.
Methods: 40 breast cancer patients with metastases were included in this study. They received TAC/TEC, CAF/CEF, NP, CAP, CMF, TFP, TA or TC regime chemotherapy, respectively. Totally 120 serum samples were collected from the patients at three time points: before chemotherapy, the end of 1 and 5-6 chemotherapy cycles, and analyzed for VEGF and ES levels using ELISA. Tumor agiogenesis activity was evaluated by serum soluble vascular cell adhesion molecule (VCAM - 1) measured by ELISA as a surrogate marker.
Results: (1) Before chemotherapy, the median level of VEGF in patients with breast cancer was 496.6 pg/ml, 4.7 times higher than that of healthy controls (P <0.001). The median level of ES was 95.5 ng/ml, 18.3% lower than that of healthy controls (P = 0.183). VCAM-1 was 1077.1 ng/ml and higher than that of controls (P <0.001). The serum VEGF levels correlated with VCAM-1 levels, tumor staging and metastatic sites (P <0.05). (2) At the end of 1 cycle of chemotherapy, the serum VEGF level (median 524.8 pg/ml) was higher than the pretreatment values (P = 0.047), whereas the levels of ES and VCAM-1 were not significantly altered (110.5 ng/ml, P = 0.055; and 975.6 ng/ml, P = 0.27). (3) At the end of 5-6 cycles, the changes in VEGF correlated with the response to chemotherapy. Serum VEGF levels in 27 patients with chemotherapy-responsive and stable disease showed a significant decrease (median 287.4 pg/ml) , but not observed in 13 patients with progressive disease. VCAM-1 also showed a treatment-related change like VEGF. However, chemotherapy might only have a minor effect on ES, because there was no significant difference in the ES levels among 5-6 cycle patients, 1 cycle patients and healthy controls, and neither between therapy-responsive patients.
Conclusion: Intensive chemotherapy for breast cancer results in a significant decrease of serum VEGF level, which might be an indicator of the controlled disease status, and following the treatment-induced response or stabilization, the tumor angiogenesis seems to change into an anti-angiogenesis direction.