13121 Purpose: To determine whether UGT1A1, UGT1A7, and UGT1A9 polymorphisms affect pharmacokinetics (PK) of irinotecan and treatment outcome of Korean patients with advanced non-small cell lung cancer (NSCLC). Methods: Eighty-one patients with advanced NSCLC were treated with irinotecan and cisplatin chemotherapy. Genomic DNA was extracted from peripheral blood and genotyped using direct sequencing. We analyzed the association of UGT1A genotypes with irinotecan PK and clinical outcomes. Results: In genotype-PK association analysis, UGT1A1*6/*6 (n = 6), UGT1A7*3/*3 (n = 6) and UGT1A9–118(dT)9/9 (n = 11) were associated with significantly lower AUCSN-38G/AUCSN-38 ratio (P = 0.002, 0.009and 0.001, respectively). In linkage disequilibrium (LD) analysis, the UGT1A7 variants were highly linked with UGT1A1*6 (D` = 0.85, r2 = 0.63) and UGT1A9*22 (D` = 0.95, r2 = 0.88), which was substantiated in haplotype analysis. Patients with UGT1A1*6/*6 had lower tumor response and higher incidence of severe neutropenia. UGT1A9–118(dT)9/9 also showed a trend for high incidence of severe diarrhea, but not tumor response. In survival analysis, patients with UGT1A1*6/*6 had significantly shorter progression-free survival (P = 0.001) and overall survival (P = 0.017). Conclusions: These findings suggest that UGT1A1*6 and UGT1A9*22 genotypes may be important for SN-38 glucuronidation and associated with irinotecan-related severe toxicity. Specifically, UGT1A1*6 might be useful for predicting tumor response and survival outcome of Korean patients with NSCLC treated with irinotecan-based chemotherapy. (Supported in part by NCC Grant 0210130 and 0510080 from National Cancer Center, Korea). No significant financial relationships to disclose.
Background: The biologic behavior of metaplastic breast cancer (MBC) has not been well elucidated due to its rarity and heterogeneity. This study was designed to assess the clinical and tumor characteristics and outcomes of MBC patients as compared with invasive ductal carcinoma (IDC) in general and the triple-negative (TN) subtype.Materials and methods: This study included 35 MBC and 2,839 IDC patients diagnosed at the National Cancer Center, Korea between 2000 and 2008. We, retrospectively, reviewed the clinicopathologic characteristics and clinical outcomes.Results: The mean age was 47.4 years for MBC group and 48.3 years for IDC group. The MBC group presented with larger tumors (≥ T2, 78.8% vs 41.0%; P<0.001), higher histologic grade (grade 3, 92.0% vs 44.6%; P<0.001), fewer ER and PgR positivity (ER+, 14.3% vs 69.0% ; P<0.001 and PgR+, 25.7% vs 66.1%; P<0.001), higher Ki-67 expression (35.5%±26.2% vs 20.6% ±19.8%; P=0.024) and more TN subtypes (48.6% vs 11.9%; P<0.001) than IDC group. Excluding de novo stage IV patients, 14 of 32 (43.7%) MBC patients and 260 of 2782 (9.4%) IDC patents developed disease recurrence with a median follow-up of 36.2 months (range, 4.9-117.8 months). MBC was a poor prognostic factor for disease recurrence in univariate and multivariate analysis (HR 5.19; 95% CI, 2.04-13.18; P=0.001). MBC patients demonstrated aggressive pathologic features and experienced more disease recurrence (HR 4.77; 95% CI, 1.99-11.44; P=0.001) even when compared with 330 patients with TN subtype.Conclusions:Patients with metaplastic breast carcinoma appeared to have inherent aggressive tumor biology with poorer clinical outcomes than those with IDC in general and TN subtype.Partly supported by NCC Grant No 0610240
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4057.
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