Clinical Trial Of A New Regimen As Neoadjuvant Chemotherapy For Breast Cancer Patients And Translational Study For The Prediction Of Efficacy

Neoadjuvant chemotherapy is the first choice for the LABC patients.However,the same treatment shows different outcome in different subtypes of breast cancer.How to improve the effect of chemotherapy and predict the respose are still neeed to be further researched.OBJECTIVES: To investigate the efficacy and safety of the weekly paclitaxel combined with cisplatin as neoadjuvant chemotherapy in LABC.The changes of peripheral blood immune cells induced by chemotherapy will be invstigated.To find the possible preditors which may be associated with the response to the chemotherapy.METHODS: 1)Patients with LABC will be enrolled in the clinical trial and receive the weekly paclitaxel combained with cisplatin.Efficacy and safety will be investigated.2)Compare the expression of different immune cells in peripheral blood before and after neoadjuvaney treatment through the flow cytometry.The association between immune cells and response to treatment will be estimated.3)The correlationship will be analysis between the SNPs which are associated with response to paclitaxel or cisplatin and the response to neoadjuvant treatment.We are looking for the possible genes which make the same hormone receptor positive breast cancers show different respose to the therapy through the second-generation sequencing.RESULT: 1)The neoadjuvant chemotherapy of weekly paclitaxel and cisplatin had a total p CR rate of 34.4%,24.7% for luminl breast caner patients,64.7% for triple negatve ones and 54.2% for HER2 positive ones.Multivariate analysis showed that the use of trastuzumab,lack of ER expression and high Ki67 expression were the independent impactors for p CR.2)ER status,HER2*B cell and HER2* NK cells were independent predictors of p CR.3)ABCB1 haplotype was associated with the effect of neoadjuvant chemotherapy.Patients with ABCB1 2677GG+3435CC were more likely to obtain pCR. After adjusted the age,tumor size,lymph node status,HR expression and ki67,ABCB1 haplotye and high ki67 is and independent predictor of p CR.4)The mutations in MAP3 KI,AKT1 and ATM genes in Luminal breast cancers may be associated with drug resistance,and MRE11 A mutatuion may cause the tumor to be sensitive to the chemotherapy.CONCLUSION: 1)The weekly paclitaxel combined with cisplation as neoadjuvant chemotherapy can improve the pc R rate of patients with LABC which has less side effects and can be well torlerated.This regimen might be considered as a optinal neoadjuvant chemotherapy.2)The interaction of B cells and NK cells with HER2 impacted the neoadjuvant chemotherapy sensitiviy in breast caners.3)ABCB1 genotpye can be used as a predictor of paclitaxel and cisplatin in patients with LABC,providing surport for individual therapy.4)MRE11A and other genes may affect the response to paclitaxel and cisplatin in luminal breast caners,and the mechanisms need to be further studied.