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

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 C...

Full description

Saved in:
Bibliographic Details
Published in:The pharmacogenomics journal 2016-10, Vol.16 (5), p.472-477
Main Authors: 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, Guarneri, V
Format: Article
Language:English
Subjects:
Adult
Aged
Alleles
Analysis
Antibody-dependent cell-mediated cytotoxicity
Antineoplastic Combined Chemotherapy Protocols - adverse effects
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biomarkers, Tumor - analysis
Biomarkers, Tumor - genetics
Breast cancer
Breast Neoplasms - drug therapy
Breast Neoplasms - enzymology
Breast Neoplasms - genetics
Breast Neoplasms - immunology
Care and treatment
Chemotherapy
Chemotherapy, Adjuvant
Clinical Trials, Phase II as Topic
Cytotoxicity
Development and progression
Disease-Free Survival
ErbB-2 protein
Female
Gene Frequency
Genetic aspects
Genetic polymorphisms
Genotype
Genotyping
Health aspects
Humans
Immunoglobulin G
Immunoglobulins
Lapatinib
Lymphocytes
Mastectomy
Methods
Middle Aged
Neoadjuvant Therapy
Patient outcomes
Pharmacogenetics
Pharmacogenomic Testing
Pharmacogenomic Variants
Phenotype
Polymorphism, Single Nucleotide
Protein Kinase Inhibitors - adverse effects
Protein Kinase Inhibitors - therapeutic use
Quinazolines - adverse effects
Quinazolines - therapeutic use
Randomized Controlled Trials as Topic
Receptor, ErbB-2 - analysis
Receptors, IgG - genetics
Retrospective Studies
Time Factors
Trastuzumab
Trastuzumab - adverse effects
Trastuzumab - therapeutic use
Treatment Outcome
Tumor-infiltrating lymphocytes
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1470-269X
1473-1150
DOI:10.1038/tpj.2016.51