1. Immunoglobulin G fragment C receptor polymorphisms and efficacy of preoperative chemotherapy plus trastuzumab and lapatinib in HER2-positive breast cancer
- Author
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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, A, Conte, P F, and Guarneri, V
- Abstract
Lapatinib enhances antibody-dependent cell-mediated cytotoxicity (ADCC) activity of trastuzumab. Fc?Rpolymorphisms have been associated with both ADCC and clinical activity of trastuzumab in HER2+ breast cancer (BC) patients (pts). We analyzed Fc?RIIa-H131R and Fc?RIIIa-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 Fc?RIIIaV 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 Fc?RIIIaV 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 Fc?RIIapolymorphism, and between pre-treatment tumor-infiltrating lymphocytes and Fc?Rpolymorphisms. Our study provides evidence for a Fc?RIIIaV allele-restricted pCR benefit from neoadjuvant trastuzumab plus lapatinib in HER2+ BC.
- Published
- 2016
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