ABCB1, FCGR2A, and FCGR3A polymorphisms in patients with HER2-positive metastatic breast cancer who were treated with first-line taxane plus trastuzumab chemotherapy

Abstract

The aim of this study was to elucidate clinical implications of ABCB1, FCGR2A, and FCGR3A polymorphisms in patients with HER2-positive metastatic breast cancer (MBC) after taxane plus trastuzumab (TH) chemotherapy. Using genomic DNA samples extracted from mononuclear cells of consecutive patients with HER2-positive MBC who received first-line TH, we analyzed five polymorphisms (ABCB1 1236C>T, ABCB1 2677G>T/A, ABCB1 3435C>T, FCGR2A 131H/R, and FCGR3A 158V/F), and then correlated them with response rate (RR), progression-free survival (PFS), overall survival (OS), and adverse events of patients. A total of 57 women were analyzed. The median age was 46 years (range, 27-72 years). ABCB1 2677T carriers had a longer PFS (p=0.037) along with a tendency toward a longer OS (p=0.057). ABCB1 3435CC genotype carriers had a shorter PFS (p=0.039) along with a tendency toward a shorter OS (p=0.093). In combined analysis, PFS was significantly longer in ABCB1 1236CC and/or 2677TT carriers compared to the others (p=0.006). FCGR2A 131H/R and FCGR3A 158V/F polymorphisms were not significantly associated with RR, PFS, and OS. In conclusion, our data support that ABCB1 1236C>T, 2677G>T/A, and 3435C>T polymorphisms may predict PFS after first-line TH chemotherapy in patients with HER2-positive MBC. In contrast, FCGR2A 131H/R and FCGR3A 158V/F polymorphisms were not significantly correlated to clinical outcomes after TH chemotherapy. Further studies with a more statistical power are necessary to validate our findings.