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.
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.
Immunoglobulin G fragment C receptor polymorphisms and efficacy of preoperative chemotherapy plus trastuzumab and lapatinib in HER2-positive breast cancer / Musolino, A; Naldi, N; Dieci, Maria Vittoria; Zanoni, Daniele; Rimanti, Anita; Boggiani, D; Sgargi, P; Generali, Dg; Piacentini, Federico; Ambroggi, M; Cagossi, K; Gianni, L; Sarti, S; Bisagni, G; Ardizzoni, Andrea; Conte, Pf; Guarneri, Valentina. - In: PHARMACOGENOMICS JOURNAL. - ISSN 1470-269X. - 16:5(2016), pp. 472-477. [10.1038/tpj.2016.51]
Data di pubblicazione: | 2016 | |
Data di prima pubblicazione: | 5-lug-2016 | |
Titolo: | Immunoglobulin G fragment C receptor polymorphisms and efficacy of preoperative chemotherapy plus trastuzumab and lapatinib in HER2-positive breast cancer | |
Autore/i: | Musolino, A; Naldi, N; Dieci, Maria Vittoria; Zanoni, Daniele; Rimanti, Anita; Boggiani, D; Sgargi, P; Generali, Dg; Piacentini, Federico; Ambroggi, M; Cagossi, K; Gianni, L; Sarti, S; Bisagni, G; Ardizzoni, Andrea; Conte, Pf; Guarneri, Valentina | |
Autore/i UNIMORE: | ||
Digital Object Identifier (DOI): | http://dx.doi.org/10.1038/tpj.2016.51 | |
Rivista: | ||
Volume: | 16 | |
Fascicolo: | 5 | |
Pagina iniziale: | 472 | |
Pagina finale: | 477 | |
Codice identificativo ISI: | WOS:000384035000008 | |
Codice identificativo Scopus: | 2-s2.0-84977125803 | |
Codice identificativo Pubmed: | 27378608 | |
Citazione: | Immunoglobulin G fragment C receptor polymorphisms and efficacy of preoperative chemotherapy plus trastuzumab and lapatinib in HER2-positive breast cancer / Musolino, A; Naldi, N; Dieci, Maria Vittoria; Zanoni, Daniele; Rimanti, Anita; Boggiani, D; Sgargi, P; Generali, Dg; Piacentini, Federico; Ambroggi, M; Cagossi, K; Gianni, L; Sarti, S; Bisagni, G; Ardizzoni, Andrea; Conte, Pf; Guarneri, Valentina. - In: PHARMACOGENOMICS JOURNAL. - ISSN 1470-269X. - 16:5(2016), pp. 472-477. [10.1038/tpj.2016.51] | |
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