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Fc-Gamma receptor polymorphism and gene expression of peripheral blood mononuclear cells in patients with HER2-positive metastatic breast cancer receiving single-agent trastuzumab

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Abstract

Aim

The aim of this study was to investigate gene expression in the peripheral blood mononuclear cells (PBMCs) of patients with HER2-positive breast cancer receiving trastuzumab. We also evaluated the effect of Fc-gamma receptor genotype on trastuzumab-driven gene expression.

Materials and methods

Gene expression was assessed by microarray analyses before and after administration of single-agent trastuzumab in 34 patients with metastatic HER2-positive breast cancer who were genotyped for Fc-gamma receptor (FcGR) IIA H131R and FcGRIIIA V158F. Gene set enrichment analysis (GSEA) was used to identify the gene sets that were significantly enriched after administration of trastuzumab in patient cohorts categorized by FcGR variant.

Results

At baseline three non-immune-related gene sets were identified only in patient cohort of FcGRIIA non-H/H variant. Thirty gene sets were identified in the cohort of FcGRIIIA V/V variants, while no gene set was identified in FcGRIIIA non-V/V variants one week after starting trastuzumab. Eleven gene sets were identified in FcGRIIA H/H variants 8 week after starting trastuzumab, but none in non-H/H variants. Immune-related gene sets were significantly down-regulated after administration of trastuzumab.

Conclusion

The response of PBMCs to trastuzumab markedly varied with polymorphisms in FcGRIIA and FcGRIIIA. These results indicate that FcGR polymorphisms contribute to the systemic immune reaction triggered by trastuzumab. Further investigations are needed to clarify the biological effects of FcGR variation on the mechanism of trastuzumab activity.

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Acknowledgments

This study was financially supported by Health and Labor Grants for Research in Advanced Medical Oncology (H17-pharmaco-006). We would like to thank Editage (www.editage.jp) for English language editing.

Conflict of interest

The authors have no conflicts of interest to declare.

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Authors and Affiliations

  1. Department of Breast and Medical Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Chikako Shimizu, Harukaze Yamamoto, Kenji Tamura & Yasuhiro Fujiwara

  2. Department of Bioinformatics, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-0034, Japan

    Chikako Shimizu, Kaoru Mogushi, Masaki Suimye Morioka & Hiroshi Tanaka

Authors
  1. Chikako Shimizu
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  2. Kaoru Mogushi
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  3. Masaki Suimye Morioka
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  4. Harukaze Yamamoto
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  5. Kenji Tamura
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  6. Yasuhiro Fujiwara
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  7. Hiroshi Tanaka
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Corresponding authors

Correspondence to Chikako Shimizu or Masaki Suimye Morioka.

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Shimizu, C., Mogushi, K., Morioka, M.S. et al. Fc-Gamma receptor polymorphism and gene expression of peripheral blood mononuclear cells in patients with HER2-positive metastatic breast cancer receiving single-agent trastuzumab. Breast Cancer 23, 624–632 (2016). https://doi.org/10.1007/s12282-015-0614-y

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  • DOI: https://doi.org/10.1007/s12282-015-0614-y

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