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

Author

Nadia Naldi, Katia Cagossi, Federico Piacentini, Daniela Boggiani, Antonino Musolino, Daniele Zanoni, Luca Gianni, Daniele Generali, Anita Rimanti, Pierfranco Conte, P. Sgargi, Maria Vittoria Dieci, Valentina Guarneri, Massimo Ambroggi, Samanta Sarti, Giancarlo Bisagni, Andrea Ardizzoni, Musolino, GIUSEPPE ANTONIO, Naldi, N., Dieci, M. V., Zanoni, D., Rimanti, A., Boggiani, D., Sgargi, P., Generali, Daniele, Piacentini, F., Ambroggi, M., Cagossi, K., Gianni, L., Sarti, S., Bisagni, G., Ardizzoni, A., Conte, P. F., Guarneri, V., Musolino, A, Generali, D. G., and Ardizzoni, Andrea

Subjects
0301 basic medicine, Oncology, Time Factors, Pharmacogenomic Variants, Receptor, ErbB-2, Pharmacology, Immunoglobulin G, 0302 clinical medicine, Gene Frequency, Trastuzumab, HER2 Positive Breast Cancer, Antineoplastic Combined Chemotherapy Protocols, Preoperative chemotherapy, skin and connective tissue diseases, Receptor, Mastectomy, Randomized Controlled Trials as Topic, biology, Middle Aged, Neoadjuvant Therapy, Phenotype, Treatment Outcome, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Molecular Medicine, Female, medicine.drug, Adult, medicine.medical_specialty, Genotype, Genetics, Breast Neoplasms, Lapatinib, Polymorphism, Single Nucleotide, Disease-Free Survival, 03 medical and health sciences, Breast cancer, Clinical Trials, Phase II as Topic, Genetic, Internal medicine, mental disorders, medicine, Biomarkers, Tumor, Humans, neoplasms, Protein Kinase Inhibitors, Aged, Retrospective Studies, business.industry, Receptors, IgG, medicine.disease, Molecular medicine, Pharmacogenomic Testing, 030104 developmental biology, Pharmacogenetics, biology.protein, Quinazolines, business
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.

Published
2016

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