Immunoglobulin G Fragment C Receptor Polymorphisms in Solid Tumors

To the EditorFCGR3A and FCGR2A gene polymorphisms have been associated with differential binding affinity to IgG and with prediction of response to monoclonal antibody (mAb) therapy. Gavin and colleagues performed a retrospective evaluation of these polymorphisms in a randomized trial of adjuvant chemotherapy with or without trastuzumab (anti-ERBB2/HER2 mAb) in patients with surgically resected node-positive, HER2-positive breast cancer. As expected, they observed that homozygous low-affinity FCGR3A-158 phenylalanine/phenylalanine (F/F) patients received less benefit from trastuzumab than patients with higher-affinity alleles (valine [V]/F or V/V). However, in an exploratory analysis in the nontrastuzumab control arm, patients with FCGR3A-158 V/F or V/V had worse prognosis than patients with F/F. The authors moreover suggested that the differential binding affinity of FCGR proteins to intrinsic antibodies may result in differential benefit from chemotherapy alone.

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