Immunoglobulin G fragment C receptor polymorphisms and efficacy of preoperative chemotherapy plus trastuzumab and lapatinib in HER2-positive breast cancer

none17noLapatinib enhances antibody-dependent cell-mediated cytotoxicity (ADCC) activity of trastuzumab. FcγR polymorphisms have been associated with both ADCC and clinical activity of trastuzumab in HER2+ breast cancer (BC) patients (pts). We analyzed FcγRIIa-H131R and FcγRIIIa-V158F polymorphisms in the CHER-LOB trial population of HER2+ BCs treated with preoperative chemotherapy plus trastuzumab (arm A), lapatinib (arm B) or both (arm C). Genotyping was successfully performed in 73/121 (60%) pts. A significant improvement in pathological complete response (pCR) rate was observed for the combination arm C, but only in FcγRIIIa V allele carriers (C vs A, 67 vs 27%, P=0.043; C vs B, 67 vs 22%, P=0.012). An independent interaction between arm C and FcγRIIIa V allele was found for pCR (odds ratio=9.4; 95% confidence interval, 2.3-39.6; P=0.003). No significant associations were observed between pCR and FcγRIIa polymorphism, and between pre-treatment tumor-infiltrating lymphocytes and FcγR polymorphisms. Our study provides evidence for a FcγRIIIa V allele-restricted pCR benefit from neoadjuvant trastuzumab plus lapatinib in HER2+ BC.noneMusolino, A; Naldi, N.; Dieci, M. V.; Zanoni, D.; Rimanti, A.; Boggiani, D.; Sgargi, P.; Generali, D. G.; Piacentini, F.; Ambroggi, M.; Cagossi, K.; Gianni, L.; Sarti, S.; Bisagni, G.; Ardizzoni, Andrea; Conte, P. F.; Guarneri, V.Musolino, A; Naldi, N.; Dieci, M. V.; Zanoni, D.; Rimanti, A.; Boggiani, D.; Sgargi, P.; Generali, D. G.; Piacentini, F.; Ambroggi, M.; Cagossi, K.; Gianni, L.; Sarti, S.; Bisagni, G.; Ardizzoni, Andrea; Conte, P. F.; Guarneri, V