[Effects of chemotherapy on circulating angiogenic factor levels in patients with breast cancer].
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.


CONCLUSIONS
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.
Tang
Jin-hai
JH
Department of Surgery, Jiangsu Tumor Hospital, Nanjing 210009, China.
Zhao
Jian-hua
JH
Gong
Jian-ping
JP
Qin
Jian-wei
JW
Pan
Li-qun
LQ
Xu
Zhi-yin
ZY
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000097:blood / Q000188:drug therapy / Q000556:secondary; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000097:blood* / Q000188:drug therapy / Q000556:secondary; D043169:Endostatins / Q000097:blood; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000188:drug therapy / Q000556:secondary; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy / Q000556:secondary; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D012074:Remission Induction; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
D043169:Endostatins; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A