关键词: 乳腺癌, 胸苷磷酸化酶, 卡培他滨, 遗传变异, 疗效

Abstract:

AIM: To investigate the effect of thymidine phosphorylase genetic variation the (TYMP) prognosis of Her2 negative metastatic breast cancer patients treated with capecitabine based first line chemotherapy. METHODS: For retrospective analysis, 215 patients with metastatic breast cancer who were diagnosed as Her2 negative and received capecitabine-based first-line treatment in the Department of Mammary and Oncology, Beijing Tiantan Hospital Affiliated to Capital Medical University between January 2010 and December 2017 were enrolled in the study. The patients' peripheral blood was collected for TYMP gene mutation site typing, and the patients' biological specimens were retained for gene expression determination. The prognostic data were obtained by telephone follow-up. Kaplan-Meier survival analysis was used to analyze the association between different genotypes and prognosis, and Cox model was used to correct other variables.RESULTS:The genetic variation included in this study wAS collected in the NCBI database with the minor allele frequency >10% in Chinese population. Of the variations analyzed, only 1412C>T was of clinical significance. The prevalence of 1412C>T in analysis population were as follows: CC 137 cases (63.72%), CT 70 cases (32.56%), TT 8 cases (3.72%), minor allele frequency of 1412C>T is 0.20, the distribution of genetic variation were in accordance with Hardy-Weinberg Equilibrium (P=0.798). The efficacy analysis of patients with CT/TT and CC genotypes found that Objective remission rates (ORR) were 56.41% and 40.15% (P=0.021). And median progression-free survival (mPFS) was 11.5 and 7.6 months, respectively (P=0.001). Furthermore, the median overall survival (mOS) of the two genotypes was 26.6 and 24.7 months, respectively (P=0.022). After the analysis in Cox proportional hazards model for PFS, CT/TT was an independent factor for PFS (OR=0.56, P=0.011). Additionally, of the 87 postoperative tissue specimens, the results showed that the mRNA expression of TYMP in cancer tissues of the patients with CT/TT and CC genotype were significant difference (P<0.001). CONCLUSION: The clinical outcomes of Her 2 negative metastatic breast cancer patients receiving capecitabine based first line chemotherapy may be influenced by TYMP 1412C>T genetic variation through mediating the mRNA expression of TYMP.

Key words: breast cancer, thymidine phosphorylase, capecitabine, genetic variation, efficacy