The FCGR3A-158 polymorphism may be predictive of trastuzumab efficacy in patients with early-stage ERBB2/HER2-positive breast cancer, with trastuzumab being less efficacious in those who are homozygous for the low-affinity allele, according to a study published in JAMA Oncology.1                                                 

Preclinical studies suggest that single nucleotide polymorphisms (SNP) in FCGR3A and FCGR2A may be associated with varying response to the anti-HER2 monoclonal antibody trastuzumab in patients with ERBB2/HER2-positive breast cancer.

To evaluate the effect of FCGR3A and FCGR2A SNPs on trastuzumab efficacy in the adjuvant treatment of ERBB2/HER2-positive breast cancer, investigators analyzed data from 1251 patients with surgically resected node-positive, early-stage disease who participated in the phase 3 NSABP (National Surgical Adjuvant Breast and Bowel Project B-31 trial; Identifier: NCT00004067).

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In NSAPB B-31, patients receive doxorubicin plus cyclophosphamide followed by paclitaxel with or without trastuzumab weekly for 1 year.

After a median follow-up of 8.2 years, results showed that disease-free survival probability at 3, 5, and 8 years was 74% (95% CI, 71-79), 66% (95% CI, 62-71), and 58% (95% CI, 54-63) in patients who received chemotherapy alone, respectively. Among those who received chemotherapy and trastuzumab, disease-free survival was 86% (95% CI, 83-89), 82% (95% CI, 79-85), and 78% (95% CI, 74-81) at 3, 5, and 8 years, respectively.

Researchers found that adding trastuzumab significantly reduced the risk of relapse by 54% (hazard ratio [HR], 0.46; 95% CI, 0.37-0.57; P < .001).

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Patients with genotypes FCB3A-158V/V or FCB3A-158V/F achieved greater benefit from trastuzumab (HR, 0.31; 95% CI, 0.22-0.43; P < .001) than patients who were homozygous for phenylalanine at this position (HR, 0.71; 95% CI, 0.51-1.01; P = .05).

In contrast with previous reports, the findings indicate that trastuzumab may be less efficacious in patients homozygous for the low affinity allele of FCGR3A. Additional studies are needed to validate these results.


  1. Gavin PG, Song N, Kim SR, et al. Association of polymorphisms in FCGR2A and FCGR3A with degree of trastuzumab benefit in the adjuvant treatment of ERBB2/HER2–positive breast cancer. JAMA Oncol. 2016 Nov 3. doi: 10.1001/jamaoncol.2016.4884 [Epub ahead of print]