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Pharmacogenomics J. 2016 Oct;16(5):472-7. doi: 10.1038/tpj.2016.51. Epub 2016 Jul 5.

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

Author information

1
Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
2
Division of Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy.
3
Department of Oncology, Guastalla Hospital, Guastalla, Italy.
4
U.O. Multidisciplinare di Patologia Mammaria, A.O. Istituti Ospitalieri di Cremona, Cremona, Italy.
5
Medical Oncology Unit, Modena University Hospital, Modena, Italy.
6
Medical Oncology Unit, Hospital of Piacenza, Piacenza, Italy.
7
Medical Oncology Unit, Ramazzini Hospital, Carpi, Italy.
8
Medical Oncology Unit, Ospedale Infermi, Rimini, Italy.
9
Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
10
Medical Oncology Unit, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy.
11
Division of Oncology, S.Orsola-Malpighi Hospital, Bologna, Italy.

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.

PMID:
27378608
DOI:
10.1038/tpj.2016.51
[Indexed for MEDLINE]

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