Correlation Of Polymorphism C3435T Of The MDR1 Gene And The Response Of Epirubicine Containing Postoperative Adjuvant Chemotherapy In Women With Breast Cancer And Analysis Of Prognosis

Objective:To evaluate the relationship between polymorphism C3435T of the MDR1 gene and epirubicine containing regimens as postoperative adjuvant chemotherapy for breast cancer and detect prognositic factors.Methods:We observed the 5-year disease free survival (DFS) and adverse effect in breast cancer patients treated by epirubicine based postoperative chemotherapy from April 10th, 2003 to December 20th, 2005 and detected MDR1 gene codon 3435 genetic polymorphism by using real time polymerase chain reaction (RT-PCR). The relationship between genetic polymorphisms and survival after epirubicine based chemotherapy were analyzed by SPSS 13.0, and an analysis on possible prognostic factors was conducted.Results:(1) Genotype frequenciesAmong all 302 patients, the genotypes of MDR1 codon C3435T were C/C 122(40.4%), C/T 135(44.7%) and T/T 45(13.9%), respectively.(2) Genotype and survivalThe 5-year disease free survival (DFS) rate in all 302 patients was 85.1%. Patients with C/C genotype in MDR1 codon 3435 had a longer 5-year DFS (91.0%) than those with C/T (83.0%) and T/T (75.6%).151 patients were treated with 5-fluorouracil / epirubicine / cyclophosphamide (FEC) regimen, 49 patients with vinorelbine/ epirubicine (NE), 70 patients with paclitaxel/ epirubicine (TE) and 32 patients with paclitaxel/ epirubicine/ cyclophosphamide (TEC) regimen. 5-year DFS rates of patients treated by FEC, NE,TE and TEC regimens were 81.5%, 85.7%, 90.0% and 90.6%, respectively.(3) Chemotherapy related adverse effectAdverse effects of grade III or more include bone marrow suppression, gastrointestinal reaction and cardiac accident were respectively 37.1%, 25.2% and 0.6% in the cases with FEC regimen, 34.7%, 18.4% and 0.0% in the cases with NE regimen, 38.6%, 17.1% and 0.0% in the cases with TE regimen, and 37.5%, 18.8% and 3.1% in the cases with TEC regimen.(4) Prognostic factorsBy univariate analysis, there were statistically significant differences in the 5-year DFS rates between the patients with various T stage, lymph node metastasis, clinical stage, vascular invasion and genotypes in the MDR1 codon 3435. Multivariate Cox analysis showed clinical stage and MDR1 genotypes were the independent prognostic factors.Conclusion:FEC, NE, TE and TEC regimens with 4 to 6 courses could be proper postoperative chemotherapeutic regimens for breast cancer, and the chemotherapy related toxicity is acceptable. And these regimens could be recommended of adjuvant chemotherapy for patients with C/C genotype in MDR1 codon 3435, considering longer survival time was deteceted than patients with C/T and T/T genotype. The clinical stage and MDR1 genotypes were the independent prognostic factors for our cohort of patients.