| Objective:1. To analyze the clinical curative effect during biochemotherapy by Herceptin plus taxol(TAX) against Her-2-positive advanced breast cancer.2. To discuss the relationship between the Baseline Characteristics (age,Histology,Stage,ECOG PS,ER/PR,Baseline CEA,Baseline CA125 and Baseline CA15-3) and the PFS in the 83 patients.3. To discuss the predictive of changes in serum levels of CEA,CA125 and CA15-3 during biochemotherapy by Herceptin plus TAX against Her-2-positive advanced breast cancer and the relationship between tumor markers levels and the PFS in the 83 patients.Methods:1. Tumor markers were detected by retrospective study methods. We study and anayze 83 breast cancer patients confirmed by pathology in our hospital between June 2003 and June 2008. The ages of the 83 patients were between 28 to 68, and the median age was 49. In the 83 patients we study, there were 69 duct carcinoma.2. Tumor response was assessed according to the RECIST(Response Evaluation Criteria In Solid Tumors) response criteria:a complete response (CR) was defined as the complete disappearance of all objective evidence of disease; a partial response (PR) was defined as a reduction≥30% in the size (products of the 2 greatest perpendicular dimensions) of measurable lesions without any new lesions; progressive disease (PD) was defined as an increase≥20% in the size of known lesions or the appearance of new lesions; and stable disease (SD) was defined as all other situations. In this study, patients who achieved a CR or PR were classified with a radiologic OR, and all remaining patients were considered nonresponders. including progression (PD) and stable disease(SD). The progression-free(PFS) is defined as the time from randomization to objective tumor progression or death.3. All of the 83 patients accepted at least 2 cycles of biochemotherapy by Herceptin plus TAX project (Herceptin 4mg/kg in the first time, followed by a 6-day rest and 2mg/kg once daily continuously at least two months; TAX 135mg/m2 di, once/21d).4. The tumor markers were obtained immediately before the start of biochemtherapy and after the second course of biochemotherapy by ELISA methods.5. The data statistic software is SPSS13.0. The paired-samples t test procedure was used to compare CEA,CA125 and CA15-3 values before treatment and after the second course of biochemotherapy. Relations between categorical variables were examined by means of the chi-square test. To evaluate and compare the performance of CEA,CA125,CA15-3 response in predicting response to therapy, receiver operating characteristic(ROC) curves were constructed. The Kaplan-Meier method was applied in the Survival Analysis and the Univariate Analysis. Specifically, the product-limit method or to estimate survival probabilities, and the log-rank test was carried out to assess heterogeneity in survival within each prognostic factor. Kaplan-Meier survival probabilities also were plotted against the length of follow-up. A Cox proportional hazards regression model was used in the multivariate analysis to assess the prognostic potential of CEA,CA125 and CA15-3 adjusted for the possible confounding effect of all other factors that were included in the same model. A 2-tailed P value≤0.05 was considered statistically significant.Results:1. After two cycles of biochemotherapy, radiological objective response rate was 57.8%.2. The relationship between the Baseline Characteristics (Age,Histology,Stage,ECOG PS,ER/PR,Baseline CEA,Baseline CA125. Baseline CA15-3) and the PFS in the 83 patients were followed: Kaplan- Meier analysis showed that ECOG PS, Baseline CA15-3 were related to prognosis at all of the characteristics, and showed statistically significant.. When the ECOG PS＜2, the median PFS was 13.64m, while when the ECOG PS>2, the median PFS was only 6.23m. When the level of CA15-3 was under the baseline, the median PFS was 12.75m, while when the level of CA15-3 was higher than the baseline, the median PFS was only 8.84m. Multivariate CoxRegression analysis indicated that ECOG PS was independent prognostic factors. When ECOG PS＞2, the relative risk (RR) was 3.865.3. The research result of tumor markers about breast cancer are as follows:①After two cycles of biochemotherapy, In the OR group, the level of CEA was decrease from (26.59±5.51)ng/ml to(18.77±3.54)ng/ml, the level of CA125 was decrease from (30.52±4.51)U/ml to(27.37±4.72)U/ml, the level of CA15-3 was decrease from ((53.50±10.21)U/ml to(32.57±6.06)U/ml, all of the three tumor markers showed statistically significant.(all of the P＜0.005).Oppositely, in the NR group, It showed none statistically significant (all of the P>0.005).②A ROC curves analysis was carried out to assess the performance of declines in serum levels of CEA,CA125 and CA153 in predicting an OR to biochemotherapy. The area under the ROC curve(AUC) were 0.763 for CEA and 0.752 for CA125 and 0.816 for CA15-3. The best efficacy(combination between sensitivity and specificity) of CEA,CA125 and CA15-3 were observed for a 20% reduction,with a sensitivity of 62.5% and a specificity of 80.0% for CEA and a 24.4% reduction with a sensitivity of 60.4% and a specificity of 60.4% for CA125 and 19.37% reduction with a sensitivity of 83.3% and a specificity of 74.29% for CA15-3.③Combined with the three serum markers, the predicting value can be higher with the sensitivity of 89.58% and a specificity of 68.57%.④Based on the ROC curve analysis, a post-treatment 20%,24.4%,19.37% reduction in serum concentration was used as cut-off levels for defining a marker response, because this was the value with the best outcome in terms of sensitivity and specificity. Overall, A CEA response was achieved in 29 of 37 patients(78.4%) who had an OR and in 29 of 36 patients(80.6%) who had an OR and in 40 of 49 patients (81.6%).4. Patients who experienced a reduction 20.0% or 24.4%,19.37% in marker levels survived longer than patients with no marker response(CEA:10.0 vs.8.0;P=0.026; CA125:12.31vs8.0, P=0.010;CA15-3 11.0vs7.0, P=0.000). All of the tumor markers response were statistically significant(P<0.05).Conclusions:1. The changes in serum level of CEA could be used to predit biochemotherapy efficacy in patients with Her-2-positive advanced breast cancer.2. The changes of the serum markers CEA,CA125 and CA15-3 could be used to predicting the biochemotherapy by Herceptin plus TAX against with Her-2- positive advanced breast cancer. And if detecting all of them simultaneously, the predict value of breast cancer would be higher.3. Kaplan- Meier analysis showed that ECOG PS and Baseline CA15-3 were related to the PFS. However, the Multivariate CoxRegression analysis indicated that only ECOG PS was independent prognostic factors. It could be used to predict the PFS of the patients who was treated by biochemotherapy.4. Patients who experienced a reduction over the cut-off limit of 20.0% in CEA and 24.4% in CA125 and 19.37% in CA15-3 markers levels had longer PFS.
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