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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Analysis of Fcγ receptor IIIa and IIa polymorphisms: Lack of correlation with outcome in trastuzumab-treated breast cancer patients
Clinical Cancer Research, Volume 18, No. 12, Year 2012
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Description
Purpose: The mechanisms by which trastuzumab imparts clinical benefit remain incompletely understood. Antibody-dependent cellular cytotoxicity via interactions with Fcγ receptors (FcγR) on leukocytes may contribute to its antitumor effects. Single-nucleotide polymorphisms (SNP) in FCGR3A and FCGR2A genes lead to amino acid substitutions at positions 158 and 131, respectively, and affect binding of antibodies to FcγR such that 158V/V and 131H/H bind with highest affinity. This study aimed to determine whether high-affinity SNPs are associated with disease-free survival (DFS) among patients with HER2-positive nonmetastatic breast cancer. Experimental Design: Genomic DNA was isolated from 1,286 patients enrolled in a trial of adjuvant trastuzumab-based chemotherapy. Genotyping was conducted using Sanger sequencing and Sequenom mass spectrometry. Results: Patient samples (N = 1,189) were successfully genotyped for FCGR3A and 1,218 for FCGR2A. Compared with the overall results of the BCIRG006 study, in the subset of patients genotyped in this analysis, a less robust improvement in DFS was observed for the trastuzumab arms than control arm (HR, 0.842; P = 0.1925). When stratified for prognostic features, the HR in favor of trastuzumab was consistent with that of the overall study (HR, 0.74; P = 0.036). No correlation between DFS and FCGR3A/2A genotypes was seen for trastuzumab-treated patients (158V/V vs. V/F vs. F/F, P = 0.98; 131H/H vs. H/R vs. R/R, P = 0.76; 158V/V and/or 131H/H vs. others, P = 0.67). Conclusion: This analysis evaluating the association between FCGR3A/2A genotypes and trastuzumab efficacy in HER2-positive breast cancer did not show a correlation between FCGR3A-V/F and FCGR2A-H/R SNPs and DFS in patients treated with trastuzumab. ©2012 AACR.
Authors & Co-Authors
Hurvitz, Sara Alsterlind
United States, Los Angeles
University of California, Los Angeles
Buyse, Marc E.
Belgium, Louvain-la-neuve
International Drug Development Institute, Charleroi
Mackey, John R.
Canada, Edmonton
Cross Cancer Institute
Damaraju, Sambasivarao
Canada, Edmonton
Cross Cancer Institute
Robert, Nicholas J.
United States, Fairfax
Virginia Cancer Specialists
Valero, Vicente V.
United States, Houston
The University of Texas Md Anderson Cancer Center
Crown, John P.A.
Ireland, Dublin
St Vincent's University Hospital
Falkson, Carla Isadora
United States, Birmingham
The University of Alabama at Birmingham
Brufsky, Adam M.
United States, Pittsburgh
University of Pittsburgh Medical Center
Piénkowski, Tadeusz J.
Poland, Warsaw
Maria Sklodowska-curie National Research Institute of Oncology
Eiermann, Wolfgang
Unknown Affiliation
Arrabal-Martín, Miguel
Spain, Madrid
Hospital General Universitario Gregorio Marañón
Slamon, Dennis J.
United States, Los Angeles
University of California, Los Angeles
Timmerman, John M.
United States, Los Angeles
University of California, Los Angeles
Statistics
Citations: 102
Authors: 14
Affiliations: 11
Identifiers
Doi:
10.1158/1078-0432.CCR-11-2294
ISSN:
15573265
Research Areas
Cancer
Genetics And Genomics
Health System And Policy