MDR1/ABCB1 single nucleotide polymorphism (SNP) as a possible prognostic factor in breast cancer patients receiving docetaxel and doxorubicin neoadjuvant chemotherapy.

Abstract

585 Background: Drug resistance is a limitation of chemotherapy. Efflux transporters of the ATP-binding cassette family such as ABCB1 (p-glycoprotein) has been identified as a major determinant of chemoresistance. The objective of this study was to explore the correlation between the single nucleotide polymorphisms (SNP) in MDR1/ABCB1 gene and the clinical outcome of patients receiving neoadjuvant chemotherapy (NAC) consists of the substrates of p-glycoprotein. Methods: Stage II or III breast cancer patients who received NAC were enrolled. Patients were treated with 3 cycles of docetaxel and doxorubicin NAC. The clinical response was determined by RECIST criteria after 3 cycles of NAC, after which the patients received curative surgery. Patients who had not experience progression during the NAC, underwent additional 3 cycles of adjuvant chemotherapy with the same regimen. SNPs of MDR1/ABCB1 gene (C3435T, G2677T/A, and C1236T) were genotyped. The correlation of genetic polymorphisms of MDR1/ABCB1 and clinical outcome was analyzed. Results: A total of 216 patients were enrolled. The median age was 44 years and the median primary tumor size was 5.7 cm with 71.8% ≥ stage IIIA, 50.5 % of T3/T4, and 56.5% of N2 or 3 stage. The overall radiologic response rate (RR) was 80.1%, while 8.3% of patients achieved a pathologically complete response. After a follow-up duration of 37.3 months, median relapse-free survival (RFS) and overall survival (OS) were not reached. There was a trend toward longer OS (p = 0.051) and lower relapse rate (p = 0.160) in patients with TT genotype than in those with CC/CT genotype, although which did not reach statistical significance. Polymorphisms of G2677T/A or C1236T were not associated with clinical outcomes in terms of RR and survival. Conclusions: Our study suggested that genetic polymorphism of MDR1/ABCB1 C3435T might be associated with clinical outcomes in patients treated with neoadjuvant docetaxel/doxorubicin for stage II and III breast cancer. Further research including functional analysis and longer follow- up duration is warranted to clarify the clinical impact of MDR1 gene polymorphisms. No significant financial relationships to disclose.