Clinical Study Of Plasma VEGF Level In Postoperative Recurrent And Metastatic Breast Cancer Patients

Objective: Vascular endothelial growth factor (VEGF) is an important factor involved in angiogenesis process of most solid tumours. Many studies have reported that plasma VEGF levels are higher in primary breast cancer patients, and decrease soon after breast resection. In our investigation, the plasma VEGF levels of postoperative breast cancer patients with recurrence or distant metastasis were measured, and compared to serum CEA, CA15-3 and benign breast disease group. According to the plasma VEGF level of postoperative recurrent and metastatic breast cancer patients and its relationship with the site of recurrence and metastasis, we hope to find a new marker for the early discovery of recurrence and metastasis of postoperative breast cancer.Methods: 50 cases postoperative recurrent and metastatic breast cancer patients were selected, which diagnosed and treated in the Forth Hospital of Hebei Medical University during March 2007 to Dcember 2008. Among the total, 32 patients affected distant metastasis, 18 patients affected local recurrence (local recurrenct patients were confirmed by pathological diagnosis, distant metastatic patients were diagnosed by imaging). 20 cases benign breast disease patients were also selected as control group. ELISA was used to detect the plasma VEGF levels of postoperative recurrent and metastatic breast cancer patients and control group. Serum CEA and CA15-3 of postoperative recurrent and metastatic breast cancer patients were measured by microparticle chemiluminescence immunoassay at the same time. The results were analyzed. The clinical pathological factors, such as ER, PR, C-erbB-2 and pathological type of primary tumor were analyzed too.Results:1 The plasma VEGF levels of postoperative distant metastatic breast cancer patients group and local recurrent group were 184.82pg/ml (median, scope 57.00~805.32pg/ml) and 174.70pg/ml (median, scope 87.76~800.00pg/ml), respectively. The plasma VEGF level of benign breast disease patients was 118.89pg/ml (median, scope 41.65~280.60pg/ml). The plasma VEGF level of postoperative distant metastatic breast cancer patients group was obviously higher than that of benign breast disease control group(P=0.015), but had no difference with local recurrent group(P=0.207). There was no difference between local recurrent breast cancer patients group and benign breast disease control group(P=0.704).2 According to the metastatic site, the postoperative recurrent and metastatic breast cancer patients were divided into five groups: visceral metastasis group, bone metastasis group, visceral combined with bone metastasis group, chest wall recurrence group, regional lymph node metastasis group. The plasma VEGF levels were 182.91pg/ml(median, scope 125.94~ 285.81pg/ml), 186.73pg/ml (median, scope 57.00~805.32pg/ml), 190.76pg/ml(median, scope 126.13~288.40pg/ml), 182.91pg/ml (median, scope 87.80~245.20pg/ml) and 167.140pg/ml(median, scope 89.62~800.00pg/ml), respectively. There were no difference between them(P=0.781).3 According to the primary pathological type, the postoperative recurrent and metastatic breast cancer patients were divided into infiltrating ductal carcinoma group, infiltrating lobular carcinoma group and other type group. The plasma VEGF levels belong to them were 167.14pg/ml(median, scope 89.62~410.73pg/ml), 182.91pg/ml(median, scope 87.76~805.32 pg/ml) and 212.54pg/ml(median, scope 117.80~239.33pg/ml), respectively. There were no difference between them(P=0.378).4 The plasma VEGF levels of postoperative recurrence and metastasis breast cancer patients were no relation with the expression of ER, PR, C-erbB-2 in the tissues of primary tumor(P=0.964, P=0.867, P=0.322), and had no association with the menopausal status(P=0.806).5 The postoperative recurrent and metastatic breast cancer patients were divided into (-) group and (+) group according to the measured values below or up the upper limit of the normal reference values (VEGF<120pg/ml, CEA<5U/ml and CA15-3 <30U/ml), respectively. The positive rates of plasma VEGF,serum CEA and CA15-3 were 80%, 52% and 46%, respectively. The positive rate of plasma VEGF was obviously higher than that of serum CEA or CA15-3(P=0.003, P=0.002, respectively). The positive rates of CEA combined with CA15-3, CEA combined with VEGF, CA15-3 combined with VEGF were 76%, 90% and 88%, respectively. Although the positive rates had no difference between CEA combined with VEGF and CA15-3 combined with VEGF(P=0.749), they were both obviously higher than that of CEA combined with CA15-3(P=0.012, P=0.027, respectively), and they were both no significance compared to that of single VEGF(P=0.161, P=0.275, respectively).Conclusions:1 The plasma VEGF level of postoperative distant metastatic breast cancer patients group is obviously higher than that of benign breast disease control group, but has no statistical significance compared with which of local recurrent breast cancer patients group. There is no statistical significance between local recurrent breast cancer patients group and benign breast disease control group, which indicates that the distant metastasis tumor cells are the main source of the increased level of plasma VEGF.2 The postoperative recurrent and metastatic breast cancer patients were divided into five groups according to the metastatic sites: visceral metastasis group, bone metastasis group, visceral combined with bone metastasis group, chest wall recurrence group, regional lymph node metastasis group. The levels of plasma VEGF belong to them are no statistical significance.3 The plasma VEGF levels of postoperative recurrent and metastatic breast cancer patients are all obviously increased in different primary pathological types, including infiltrating ductal carcinoma, infiltrating lobular carcinoma and other types, but no significance was found.4 The level of plasma VEGF of postoperative recurrent and metastatic breast cancer patients has on relationship with the expressions of ER, PR, C-erbB-2 in primary tumor and menopausal status.5 The positive rate of plasma VEGF of postoperative recurrent and metastatic breast cancer patients is obviously higher than that of serum CEA and CA15-3. As a single marker, plasma VEGF is more sensitive than CEA and CA15-3 to judge the recurrence and metastasis of postoperative breast cancer, and have no significance compared to that of CEA combined with CA15-3. It is valuable to further study and clinical application.