| Objective1. Before and after treatment of her-2 negative advanced breast cancer patients, peripheral blood circulating tumor cells (CTCs) and vascular regulatory factor VEGF, TSP-1 were detected, and explore the relationship between CTCs and VEGF, TSP-1.2. Her-2 negative advanced breast cancer patients were divided into simple chemotherapy group, combined treatment group, through the comparative analysis of the two groups of patients in the treatment of efficacy and toxicity, etc.3. By comparing the two groups of patients before and after treatment of vascular regulatory factor VEGF, TSP-1 levels and peripheral blood CTCs value of the differences, to understand whether the combination treatment more than chemotherapy alone can reduce the CTCs value and its reasons.4. To explore effect predictors of chemotherapy combined with recombinant human vascular endostatin by analysising relationships between effect and clinical pathological factors,CTCs contents,VEGF, TSP-1, respectively;then to provide a reference for the future similar treatment.MethodsForty two breast cancer patients were treated in department of Internal Medicine-Oncology of Breast Cancer, Fujian Provincial Cancer Hospital were collected.They were HER-2 negative and primary treatment primary stage IV or recurrence of breast cancer metastasis.Then they were randomly divided into two groups,21 cases were in chemotherapy combined with recombinant human vascular endostatin group (combined treatment group),21 cases were chemotherapy group (chemotherapy group).Detected the expression of VEGF, TSP-1 in peripheral blood by enzyme linked immunosorbent test (ELISA) and detected CTCscontents with low cytometry at the time of seven days before treatment,seven days after two weeks treatment.Recorded side effets during the treatment and did evaluation of the effect after 2 weeks of treatment.Collected 10healthy female volunteers as control.Statistical package for Social Sciences verion 18.0 was used.Results1. Forty two patients of advanced breast cancer before treatment plasma the VEGF level (93.70 ± 9.70pg/ml) were much higher than ten cases of healthy volunteers plasma with a VEGF levels (66.72±8.92pg/ml), and the difference was statistically significant (P<0.05). The level of TSP-1 in peripheral blood of advanced breast cancer patients before treatment (389.70±20.66ng/ml) was higher than that of healthy volunteers (292.28±1.52 ng/ml), and the difference was statistically significant (P<0.05).2.42 patients with advanced breast cancer before treatment:Plasma VEGF level 93.70+ 9.70pg/ml, plasma TSP-1 level (389.70±20.66ng/ml), CTCs detection value of (24.55± 49.27), The promotion of angiogenesis factor VEGF was negatively correlated with the inhibition of angiogenesis factor TSP-1 (r=-0.486, P=0.001); Circulation tumor cells in peripheral blood had positive correlation with VEGF to promote angiogenesis(r=0.498, P=0.001). CTCs had a negative correlation with TSP-1 which had the role of inhibition angiogenesis (r=-0.368, P=0.018).After the treatment of patients above:Plasma VEGF level was(73.58±7.52pg/ml), plasma TSP-1 level was (389.70±20.66ng/ml), CTCs detection value was (7.70±5.37). VEGF and TSP-1 were negatively correlated (r=-0.607, p=0.001), CTCs and VEGF were not correlated (r=0.322, P=0.108), CTCs and TSP-1 were not correlated (r=0.083, P=0.688).3. The side effects of the two groups of patients were nausea, vomiting, diarrhea, constipation, bone marrow suppression, hand foot syndrome, abnormal liver function, hypertension, arrhythmia, etc. Side effects were mainly grade Ⅰ, the incidence rates of Ⅰ, Ⅱ in the combined treatment group were 16.9% and 10%, respectively. Ⅲ-Ⅳ degree of adverse reactions occurred in 6 cases (2.6%) and 1 cases (0.4%). The incidence of adverse reactions in chemotherapy group Ⅰ～Ⅱ degree was 18.2%,11.3%, Ⅲ-Ⅳ degree of adverse reactions occurred in 7 cases (3%),2 cases (0.9%), there was no significant difference in the incidence of side effects of the two groups (P=0.422).4. Combined treatment group:Before treatment, the plasma VEGF level (94.27±9.70pg/ml) was higher than the treatment (69.58±7.52pg/ml) and the difference was statistically significant (P=0.000); Before treatment, the plasma TSP-1 level (390.78± 14.93ng/ml) was higher than the treatment (316.77±2.52 ng/ml) and the difference was statistically significant (P=0.000); Peripheral blood CTCs level before treatment (25.43± 12.90) was higher than that after treatment (7.57±3.52), and the difference was statistically significant (P=0.000).Chemotherapy group:Before treatment, the plasma VEGF level (93.24±9.91pg/ml) was higher than the treatment (74.67± 6.26pg/ml) and the difference was statistically significant (P=0.000); Before treatment, the level of TSP-1 (388.62±25.50ng/ml) was higher than that after treatment (317.37±1.78ng/ml), and the difference was statistically significant (P=0.000); Peripheral blood CTCs level before treatment (21.57±7.80) were higher than treatment (7.90 ±3.08), and the difference between the two groups was statistically significant (P=0.000).The number of CTCs positive cases before treatment in combination therapy group was fifteen cases, after treatment, the number of CTCs positive cases was five cases. There were eleven positive cases of CTCs positive cases in chemotherapy group before treatment, six cases were treated with CTCs cases, the number of CTCs positive cases was not statistically significant (P=0.028) before and after treatment in combination therapy group and chemotherapy group.5. Statistically significant differences were found between advanced breast cancer with clinical benefit groupand patients without clinical benefit group among bone metastasis, molecular typing, VEGFand CTCs (P<0.05). There was no statistically significant difference between the two groups in ER, the age, menstruation status, soft tissue metastasis, hepatic metastasis, TSP-1 and pulmonary metastasis (P>0.05).Conclusion1. The status of vascular regulation in patients of advanced breast cancer was different from that of healthy people, the VEGF that promoted blood vessel growth was higher than healthy people, and the TSP-1 that inhibits angiogenesis were lower than that of healthy people.2. VEGF in advanced breast cancer patients to promote vascular growth and inhibition of angiogenesis of TSP-1 was negatively correlated, which were important factors to restrict each other in the mechanism of vascular balance.Both might affect the value of circulating tumor cells in peripheral blood by regulating tumor angiogenesis.3. Recombinant human endostatin could improve the efficacy of chemotherapy in patients of Her-2 negative advanced breast cancer without increasing toxicity.4. The detection of VEGF, TSP-1 and CTCs were inhibited in combination therapy group and chemotherapy group after treatment, Recombinant human endostatin might inhibit the detection of CTCs by vascular regulation.5. Low VEGF expression, CTCs negative, combined application of recombinant human endostatin and clinical pathological factors such as PR positive, without bone metastases, luminal a type, LumialB (HER-2 negative) could provide a reference for the prediction of advanced breast cancer of first-line treatment benefit situation. |
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