Association Between Expression Of Topoisomerase Ⅱα And Efficacy Of Epirubicin In Advanced Breast Cancer

Backgroud:TopoisomeraseⅡα(topoisomeraseⅡα, TopoⅡα) gene is adjacent to Her-2 gene, and both of them are located in chromosome 17 q12-21. TopoⅡαis one of the targets of the anthracyclines drugs. Anthracyclines drugs are cell cycle non-specific ones,which play a major role on the nucleus of the DNA and inhibite the synthesis and mitosis to realize the treatment. DNA replication requires topoisomerase to relax the double-strands and anthracyclines drugs can act on TopoⅡαto suppress tumor growth.It is interesting to hunt for biochemistry factors related to prognosis and treatment of breast cancer. TopoⅡαis a potential target of a variety of anti-cancer drugs. The study aims to analyze the expression of TopoⅡin advanced stage breast cancer and to explore the value in the treatment.It is hot and difficult to expore the prediction role of biological factors in cancer research. Topoisomerase is a key enzyme in DNA replication, and it is play a key role in DNA synthesis, transcription, nuclear fission , the formation of the correct chromosome structure, chromosome segregation and concentration. Studies have shown that anthracycline TopoⅡαis a potential target of anthracyclines drugs,whose reduced expression can affect the sensitivity of chemotherapy,and it may be an important predictor of clinical outcomes.Objective:(1)Whether the TopoⅡαare predictive and prognostic factors of breast cancer;(2)Relationships between the expression of TopoⅡαand the efficacy of anthracyclines drugs as first-line chemotherapy.Methods:ImmunohistochemistryUse SP immunohistochemical staining to determine the expression of TopoⅡα. All specimens were fixed in 10% formalin, embedded in paraffin, sliced by 4um in 3% H2O2 solution for 10 min, followed by adding anti-I (anti- TopoⅡα), II antibody (anti TopoⅡα), colored by DAB, with TBS as the negative control and anti-I as the positive control.Useχ2 test and log-rank test to analysis the results;Use statistical software SPSS13.0 to do statistical analysis, P <0.05 indicated significant difference.Results:(1) The expression of TopoⅡαof 200 advanced breast cancer patients was related to the number of distant metastatic sites, histological grades, ER and Her-2 expressions.(2) The expression of TopoⅡαwas higher in the anthracycline-effective group than the ineffective group; the positive group was 7.556 times (P <0.001 .) the effectiveness of the negative group. The expression of TopoⅡhad nothing to do with the effectiveness of the anthracyclines drugs unused group.(3)Both the cumulative 5-year overall survival rate and 5-year progression-free survival rate were higher in TopoⅡαpositive patients treated with anthracyclines drugs.Conclusions:The expression of TopoⅡαwas closely related to the first-line chemotherapy in patients with advanced breast cancer. The response rate was higher in the group whose regimens containing anthracycline drugs. Both the cumulative 5-year overall survival rate and 5-year progression-free survival rate were higher in TopoⅡαpositive patients treated with anthracyclines drugs.