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

Antonino Musolino, Nadia Naldi, Maria Vittoria Dieci, Daniele Zanoni, Anita Rimanti, D. Boggiani, P. Sgargi, Daniele Generali, Federico Piacentini, M. Ambroggi, Katia Cagossi, Luca Gianni, Samanta Sarti, Giancarlo Bisagni, A. Ardizzoni, Pierfranco Conte, Valentina Guarneri

Research output: Contribution to journalArticle

Abstract

Lapatinib 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.The Pharmacogenomics Journal advance online publication, 5 July 2016; doi:10.1038/tpj.2016.51.

Original languageEnglish
JournalPharmacogenomics Journal
DOIs
Publication statusAccepted/In press - Jul 5 2016

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine
  • Genetics

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    Musolino, A., Naldi, N., Dieci, M. V., Zanoni, D., Rimanti, A., Boggiani, D., Sgargi, P., Generali, D., Piacentini, F., Ambroggi, M., Cagossi, K., Gianni, L., Sarti, S., Bisagni, G., Ardizzoni, A., Conte, P., & Guarneri, V. (Accepted/In press). Immunoglobulin G fragment C receptor polymorphisms and efficacy of preoperative chemotherapy plus trastuzumab and lapatinib in HER2-positive breast cancer. Pharmacogenomics Journal. https://doi.org/10.1038/tpj.2016.51