Correlation of FcγR IIa-H131R and IIIa-V158F polymorphisms and clinical outcome of trastuzumab in both neoadjuvant and metastatic setting in patients with HER-2 positive breast cancer

Abstract

1100 Background: The antibody dependent cell mediated cytotoxicity (ADCC) affects an efficacy of Immunoglobulin G1 antibody, including trastuzumab which is a humanized anti-HER-2 monoclonal antibody, through fragment C receptor (FcγR) polymorphisms. One report suggested that allotype of two kinds of FcγR single nucleotide polymorphisms (SNPs) are associated with clinical outcome of patients (pts) with metastatic breast cancer (BC) who received combination trastuzumab with taxane. Ethnic difference was reported in frequency of these SNPs between Western and Asian pts. The objective of this prospective study was to evaluate whether these SNPs are associated with pathological complete response (pCR) in neoadjuvant (N) setting with pts who received trastuzumab based chemotherapy, and objective response (OR) in metastatic (M) setting in pts who received single trastuzumab. Methods: Eligible criteria include HER-2 positive BC, chemotherapy-naïve, measurable disease, PS 0–2 and adequate organ functions. Pts in N setting received standard FEC (5-fluorouracil/epirubicin/cyclophosphamide q3w for 4cycles followed by weekly paclitaxel/trastuzumab for 12 weeks. Pts in M setting received single trastuzumab q1w until progression. 384 SNPs of different FcγR loci were assessed from genomic DNA extracted from peripheral blood by GOLDEGATE beads array (illumina Co.). Results: Nineteen operable and 36 metastatic HER-2 positive BC pts have been enrolled in each N and M setting, respectively. pCR in N setting was 26.3%, and OR in M setting was 22.2%. The frequencies of FcγRIIa131 genotypes were H/H 43%, H/R 49%, R/R 8%, and that of FcγRIIIa158 were V/V 43%, V/F 47%, F/F 10%, respectively. 131H/H genotype was significantly correlated with pCR (p = 0.0034) and OR (p = 0.037). 158V/V genotype had a tendency to be correlated with pCR (p = 0.067) and was significantly correlated with OR (p = 0.037). The median PFS was 8.9 months for pts with 131H/H and 3.8 months for R carriers (H/R or R/R). Conclusions: Our data for the first time suggest that these two SNPs predict pCR to trastuzumab based chemotherapy in N setting, and OR to single trastuzumab in M setting. No significant financial relationships to disclose.