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

The Pharmacogenomics Journal volume 16, pages 472–477 (2016)Cite this article

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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.

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Acknowledgements

This study was supported, in part, by a grant from PGxHealth LLC/Transgenomic, which also provided technical assistance for FcγRIIa/IIIa genotype analyses. We would like to thank all participating patients and staff at CHER-LOB trial sites.

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Authors and Affiliations

  1. Medical Oncology Unit, University Hospital of Parma, Parma, Italy

    A Musolino, N Naldi, A Rimanti, D Boggiani & P Sgargi

  2. Division of Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy

    M V Dieci, P F Conte & V Guarneri

  3. Department of Oncology, Guastalla Hospital, Guastalla, Italy

    D Zanoni

  4. U.O. Multidisciplinare di Patologia Mammaria, A.O. Istituti Ospitalieri di Cremona, Cremona, Italy

    D G Generali

  5. Medical Oncology Unit, Modena University Hospital, Modena, Italy

    F Piacentini

  6. Medical Oncology Unit, Hospital of Piacenza, Piacenza, Italy

    M Ambroggi

  7. Medical Oncology Unit, Ramazzini Hospital, Carpi, Italy

    K Cagossi

  8. Medical Oncology Unit, Ospedale Infermi, Rimini, Italy

    L Gianni

  9. Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy

    S Sarti

  10. Medical Oncology Unit, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy

    G Bisagni

  11. Division of Oncology, S.Orsola-Malpighi Hospital, Bologna, Italy

    A Ardizzoni

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Correspondence to A Musolino.

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Musolino, A., Naldi, N., Dieci, M. et al. Immunoglobulin G fragment C receptor polymorphisms and efficacy of preoperative chemotherapy plus trastuzumab and lapatinib in HER2-positive breast cancer. Pharmacogenomics J 16, 472–477 (2016). https://doi.org/10.1038/tpj.2016.51

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