Abstract P2-09-36: Role of ABCB1 Polymorphisms as Predictive Markers in Patients with HER-2 FISH Positive Metastatic Breast Cancer Who Were Treated with Taxane Plus Trastuzumab First Line Chemotherapy

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Abstract Background: ABCB1 polymorphisms could predict treatment results of taxane therapy in several malignancies. FCGR2A and FCGR3A polymorphisms were associated with clinical outcomes in several diseases after treatment with monoclonal antibody drugs which had antibody-dependent cell-mediated cytotoxicity activity. These polymorphisms could be possible predictive markers after taxane plus trastuzumab (TH) chemotherapy in patients with HER-2-positive metastatic breast cancer (MBC). Methods: Fifty-seven patients with HER-2 FISH positive MBC who received TH chemotherapy as the 1st-line treatment were enrolled. We analyzed 5 polymorphisms using DNA from peripheral blood mononuclear cells: ABCB1 1236C>T (rs1128503), ABCB1 2677G>T/A (rs2032582), ABCB1 3435C>T (rs1045642), FCGR2A 131H/R (rs1801274), and FCGR3A 158V/F (rs396991), then correlated them to treatment results of patients. Results: Among 57 patients, 22 patients (38.6%) received weekly paclitaxel plus trastuzumab, 26 patients (45.6%) tri-weekly paclitaxel plus trastuzumab, and 9 patients (15.8%) tri-weekly docetaxel plus trastuzumab. After a median follow-up of 30.6 (range, 0.6-75.9) months, median progression-free survival (PFS) was 15.1 (95% confidence interval (CI), 10.3-19.8) months. ABCB1 2677T allele carriers had longer PFS than the others (42.1 (95% CI, 12.7-71.4) months vs. 13.0 (95% CI, 10.6-15.4) months; p=0.037) along with a tendency toward higher response rate (RR) (86.4% vs. 76.0%; p=0.470) and longer overall survival (OS) (54.7 (95% CI, 43.0-66.4) months vs. 38.9 (95% CI, 18.1-59.7) months; p=0.057). In addition, ABCB1 3435CC genotype carriers had shorter PFS than the others (13.0 (95% CI, 10.8-15.2) months vs. 19.1 (95% CI, 0.0-38.5) months; p=0.039) along with a tendency toward lower RR (78.6% vs. 100%; p=0.567) and shorter OS (38.9 (95% CI, 19.7-58.1) months vs. 54.7 (95% CI, 43.0-66.4) months; p=0.093). ABCB1 1236C>T, FCGR2A 131H/R, and FCGR3A 158V/F were not significantly associated with RR, PFS, and OS. None of these polymorphisms were associated with any grades of hematologic or cardiac toxicities. Conclusions: Our results support that ABCB1 2677G>T/A and 3435C>T may have predictive roles after the 1st-line TH chemotherapy in patients with HER-2-positive MBC. In contrast, ABCB1 1236C>T, FCGR2A 131H/R, and FCGR3A 158V/F could not predict response after TH treatment. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-09-36.