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Chromosome 17 centromere (CEP17) duplication as a predictor of anthracycline response: evidence from the NCIC Clinical Trials Group (NCIC CTG) MA.5 Trial

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Abstract

HER2 gene amplification and topoisomerase IIα gene (TOP2A) alteration have been associated with increased benefit from anthracycline compared to non-anthracycline containing adjuvant breast cancer chemotherapy in some but not other studies. Chromosome 17 centromere (CEP17) duplication was measured on TMAs from formalin-fixed paraffin-embedded specimens obtained from 639 of 716 premenopausal women with node positive breast cancer who received cyclophosphamide, epirubicin and fluorouracil (CEF) or cyclophosphamide, methotrexate and fluorouracil (CMF) in the randomized controlled mammary 5 (MA.5) adjuvant trial. The prognostic impact of CEP17 duplication and its interactions with treatment were studied for relapse-free survival (RFS) and overall survival (OS). Overall, CEP17 duplication was not significantly associated with RFS or OS in multivariate analysis. For patients whose tumours had normal CEP17 copy number there were no apparent benefits for CEF compared to CMF for RFS (HR 0.98; 95% CI 0.68–1.42) or OS (HR 1.10; 95% CI 0.72–1.69). For patients whose tumours had CEP17 duplication, there was significant benefit for CEF compared to CMF for RFS (HR 0.54; CI 0.33–0.89) and a trend towards significance for OS (HR 0.64; CI 0.37–1.09). The adjusted P values for interaction between treatment and CEP17 duplication were 0.09 for RFS and 0.13 for OS. This study suggests that CEP17 duplication has a borderline association with clinical responsiveness to anthracycline containing chemotherapy similar to previous results seen with HER2 amplification and TOP2A alteration in MA.5. An appropriately powered meta-analysis is required to discriminate the predictive value of these three candidate markers.

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Authors and Affiliations

  1. Sunnybrook Odette Cancer Centre, The University of Toronto, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada

    Kathleen I. Pritchard

  2. University of Toronto, Toronto, ON, Canada

    Kathleen I. Pritchard & Frances P. O’Malley

  3. Endocrine Cancer Group, Edinburgh Cancer Research Centre, Western General Hospital, Crewe Road South, Edinburgh, EH4 2XR, UK

    Alison Munro

  4. Department of Laboratory Medicine, St. Michael’s Hospital, Toronto, ON, Canada

    Frances P. O’Malley

  5. NCIC Clinical Trials Group (NCIC CTG) and Queen’s University, Kingston, ON, Canada

    Dongsheng Tu, Xiao Li & Lois Shepherd

  6. McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada

    Mark N. Levine

  7. University of British Columbia, Vancouver, BC, Canada

    Stephen Chia

  8. British Columbia Cancer Agency, Vancouver, BC, Canada

    Stephen Chia

  9. Ontario Institute for Cancer Research, Toronto, ON, Canada

    John M. S. Bartlett

Authors
  1. Kathleen I. Pritchard
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  2. Alison Munro
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  3. Frances P. O’Malley
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  4. Dongsheng Tu
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  5. Xiao Li
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  6. Mark N. Levine
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  7. Lois Shepherd
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  8. Stephen Chia
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  9. John M. S. Bartlett
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Correspondence to Kathleen I. Pritchard.

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Pritchard, K.I., Munro, A., O’Malley, F.P. et al. Chromosome 17 centromere (CEP17) duplication as a predictor of anthracycline response: evidence from the NCIC Clinical Trials Group (NCIC CTG) MA.5 Trial. Breast Cancer Res Treat 131, 541–551 (2012). https://doi.org/10.1007/s10549-011-1840-4

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  • DOI: https://doi.org/10.1007/s10549-011-1840-4

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