Abstract PD09-05: Single nucleotide polymorphism of XRCC1 which participates in DNA repair mechanism predicts clinical outcome in relapsed or metastatic breast cancer patients treated with S1 and oxaliplatin chemotherapy: Results from multicenter prospective study (TORCH_KCSG BR07-03)

Abstract

Abstract Background: S1 and oxaliplatin (SOX) combination chemotherapy is an effective regimen in anthracycline and taxane pretreated metastatic breast cancer (MBC) patients with manageable toxicities (KCSG BR07-03, SABCS 2011 #Abst P3-16-06). The aim of this study was to investigate the association of the single nucleotide polymorphisms (SNPs) and clinical outcome in MBC treated with SOX chemotherapy. Patients and Methods: A total of 87 MBC patients previously treated with or resistant to anthracycline and taxane chemotherapy were enrolled in this prospective multicenter trial. The patients received S-1 80mg/m2/day (day 1–14) and oxaliplatin 130 mg/m2 (day 1) every 3 weeks till progression. Among the 87 patients, 77 patients were available for SNP analysis. Germline DNA from peripheral blood (PB) mononuclear cells was extracted. SNPs in 4 genes from pathways that may influence cellular sensitivity to S1 and oxaliplatin (TS, ERCC, XPD, and XRCC) were genotyped from PB sample using PCR-restriction fragment length polymorphism. Results: Overall response rate (RR) was 38.5% (95% CI: 27.7–49.3) and disease control rate was 67.9% (95% CI:57.5–78.3) to SOX. Median time-to-progression (TTP) and overall survival (OS) were 6.0 mo (95% CI: 5.1–6.9 mo) and 19.4 mo (95% CI: not estimated), respectively. XRCC1 Arg194Trp SNP which participates in DNA repair mechanism showed correlation with the clinical outcome. RR was tend to higher in XRCC1 Arg194Trp CC genotype compared with CT or TT genotype (50.0 % vs 35.1% or 12.5%, P = 0.121). TTP of patients with CC genotype in XRCC1 Arg194Trp was significantly longer than the TTP of patients with CT or TT genotype (median TTP: 6.4 mo in CC, 5.9 mo in CT, 3.0 mo in TT, P = 0.007) as well as overall survival (OS) (median OS: not reached in CC, 13.9 mo in CT, 7.1 mo in TT, P = 0.006). After adjusting for hormone receptor status, performance status, and visceral involvement, prognostic value of XRCC1 Arg194Trp SNP remained significant (Hazard Ratio=1.322 and 4.484, P = 0.016). Other SNPs were not significantly associated with survival or toxicities. Conclusion: XRCC1 Arg194Trp SNP is associated with clinical outcome of MBC patients treated with SOX chemotherapy. Further studies of the relationship between germline polymorphisms in XRCC1 and functional mechanism researches are warranted. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD09-05.