Trastuzumab (Herceptin®) has been approved by the US FDA for the treatment of breast cancer patients with overexpression of ERBB2. The binding of the Fc part of Trastuzumab to the FCg receptor on NK cells results in an antibody-dependent cell-mediated cytotoxic effect (ADCC). However, polymorphisms of the FCGR3A gene encoding FCg receptors could affect the efficiency of Trastuzumab. A total of 1,251 patients with early stage ERBB2-postive breast cancer were enrolled in the phase III trial NSABP B31 to investigate the effect of FCGR3A-158 SNPs on response to Trastuzumab. The proportions of patients with the FCGR3A-158 genotypes V/V, F/V, and F/F were 12%, 42%, and 46%, respectively. Patients with the genotype V/V derived most benefit from Trastuzumab with a HR of 0.12 (95% CI, 0.05-0.28; P<0,001), followed by patients with heterozygous F/V and homozygous F/F genotype. These results suggest that the FCGR3A-158 polymorphism is a predictive marker for Trastuzumab efficacy in breast cancer patients. 

1. Publication: 

Gavin PG., et al., JAMA Oncol. Published online November 3, 2016.DOI: 10.1001/jamaoncol.2016.4884

http://jamanetwork.com/journals/jamaoncology/article-abstract/2578707

2. SNPedia:

https://www.snpedia.com/index.php/Rs396991

3. CancerNetwork:

http://www.cancernetwork.com/news/fcgr3a-polymorphisms-predict-trastuzumab-benefit-her2-positive-breast-cancer

4. Trial registration:

clinicaltrials.gov Identifier for NSABP B-31: NCT00004067

https://clinicaltrials.gov/show/NCT00004067