Predictive value of FCR polymorphisms: A further step on the long and winding road to application
Mené sur 2 119 patientes atteintes d'un cancer du sein HER2+, cet essai de phase III évalue l'association entre des polymorphismes des gènes FCGR2A et FCGR3A et le degré d'efficacité, du point de vue de la survie sans progression, de l'ajout du trastuzumab à un traitement adjuvant combinant doxorubicine et cyclophosphamide suivi de paclitaxel
The addition of the ERBB2/HER2 protein–targeting trastuzumab antibody to standard chemotherapy is a consolidated treatment for patients with ERBB2/HER2–overexpressing breast cancer. Nevertheless, the clinical benefit of trastuzumab is still limited to a proportion of patients with advanced disease (26%)1 or undergoing adjuvant treatment (50%).2 Identification of suitable biomarkers of predictive value is therefore a pressing medical need to improve patient stratification. To this end, several studies focused on the immune-related effects of trastuzumab mediated by its binding to the Fcγ receptor (FCGR) expressed by macrophages and natural killer cells, particularly antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxic effects, and antibody–mediated cellular phagocytosis. The strength of these responses was shown to correlate with the antibody-binding affinity of FCGR, which is dictated by some common single-nucleotide polymorphisms (SNPs) in the coding region of the FCGR genes.3 Functionally relevant FCGR SNPs affecting affinity for human immunoglobulins (IgG) have been demonstrated for FCGR2A and FCGR3A, with a histidine (H)/arginine (R) polymorphism at position 131 for FCGR2A and a valine (V)/phenylalanine (F) polymorphism for FCGR3A at position 158...
JAMA Oncology , commentaire, 2015