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Research Article

Association Studies of Fcγ Receptor Polymorphisms with Outcome in HER2+ Breast Cancer Patients Treated with Trastuzumab in NCCTG (Alliance) Trial N9831

Nadine Norton, Rebecca M. Olson, Mark Pegram, Kathleen Tenner, Karla V. Ballman, Raphael Clynes, Keith L. Knutson and Edith A. Perez
Nadine Norton
1Mayo Clinic, Jacksonville, Florida.
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Rebecca M. Olson
2Stanford University, Stanford, California.
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Mark Pegram
2Stanford University, Stanford, California.
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Kathleen Tenner
3Mayo Clinic, Rochester, Minnesota.
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Karla V. Ballman
3Mayo Clinic, Rochester, Minnesota.
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Raphael Clynes
4Columbia University, New York, New York.
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  • For correspondence: perez.edith@mayo.edu kknutson@vgtifl.org rc645@cumc.columbia.edu
Keith L. Knutson
3Mayo Clinic, Rochester, Minnesota.
5Vaccine and Gene Therapy Institute of Florida, Port St. Lucie, Florida.
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  • For correspondence: perez.edith@mayo.edu kknutson@vgtifl.org rc645@cumc.columbia.edu
Edith A. Perez
1Mayo Clinic, Jacksonville, Florida.
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  • For correspondence: perez.edith@mayo.edu kknutson@vgtifl.org rc645@cumc.columbia.edu
DOI: 10.1158/2326-6066.CIR-14-0059
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Abstract

Patients with HER2+ breast cancer treated with trastuzumab and chemotherapy have superior survival compared with patients treated with chemotherapy alone. Polymorphisms within FCGR2A and FCGR3A are associated with binding affinity of natural killer cells to the IgG1 portion of trastuzumab, and a polymorphism in FCGR2B (I232T) is associated with impaired regulatory activity. The association of these polymorphisms with clinical response among trastuzumab-treated patients is equivocal, with both positive and negative associations. We performed genotyping analysis on the FCGR3A V158F, FCGR2A R131H, and FCGR2B I232T polymorphisms in 1,325 patients from the N9831 clinical trial. Patients in arm A (N = 419) received chemotherapy only. Patients in arms B (N = 469) and C (N = 437) were treated with chemotherapy and trastuzumab (sequentially in arm B and concurrently in arm C). Using log-rank test and Cox proportional hazard models, we compared disease-free survival (DFS) among genotypic groups within pooled arms B/C. We found no differences in DFS between trastuzumab-treated patients who had the FCGR3A 158 V/V and/or FCGR2A 131 H/H high-affinity genotypes and patients without those genotypes. Furthermore, there was no significant interaction between FCGR3A and FCGR2A and treatment. However, there was a difference in DFS for FCGR2B I232T, with I/I patients deriving benefit from trastuzumab (P < 0.001), compared with the T carriers who did not (P = 0.81). The interaction between FCGR2B genotype and treatment was statistically significant (P = 0.03). Our analysis did not reveal an association between FcγR high-affinity genotypes and outcomes. However, it seems that the FCGR2B inhibitory gene may be predictive of adjuvant trastuzumab benefit. Cancer Immunol Res; 2(10); 1–8. ©2014 AACR.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Immunology Research Online (http://cancerimmunolres.aacrjournals.org/).

  • Prior presentation: Preliminary reports from this study were presented at the AACR Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications; 2013 Oct 3–6. San Diego, CA. Abstract nr B123.

  • Received April 2, 2014.
  • Revision received June 20, 2014.
  • Accepted June 20, 2014.
  • ©2014 American Association for Cancer Research.
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This OnlineFirst version was published on September 12, 2014
doi: 10.1158/2326-6066.CIR-14-0059

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Association Studies of Fcγ Receptor Polymorphisms with Outcome in HER2+ Breast Cancer Patients Treated with Trastuzumab in NCCTG (Alliance) Trial N9831
Nadine Norton, Rebecca M. Olson, Mark Pegram, Kathleen Tenner, Karla V. Ballman, Raphael Clynes, Keith L. Knutson and Edith A. Perez
Cancer Immunol Res September 12 2014 DOI: 10.1158/2326-6066.CIR-14-0059

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Association Studies of Fcγ Receptor Polymorphisms with Outcome in HER2+ Breast Cancer Patients Treated with Trastuzumab in NCCTG (Alliance) Trial N9831
Nadine Norton, Rebecca M. Olson, Mark Pegram, Kathleen Tenner, Karla V. Ballman, Raphael Clynes, Keith L. Knutson and Edith A. Perez
Cancer Immunol Res September 12 2014 DOI: 10.1158/2326-6066.CIR-14-0059
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