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Breast Cancer Research and Treatment

, Volume 131, Issue 2, pp 541–551 | Cite as

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

  • Kathleen I. Pritchard
  • Alison Munro
  • Frances P. O’Malley
  • Dongsheng Tu
  • Xiao Li
  • Mark N. Levine
  • Lois Shepherd
  • Stephen Chia
  • John M. S. Bartlett
Clinical trial

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.

Keywords

Chromosome Centromere CEP17 Duplication Anthracycline 

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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Kathleen I. Pritchard
    • 1
    • 2
  • Alison Munro
    • 3
  • Frances P. O’Malley
    • 2
    • 4
  • Dongsheng Tu
    • 5
  • Xiao Li
    • 5
  • Mark N. Levine
    • 6
  • Lois Shepherd
    • 5
  • Stephen Chia
    • 7
    • 8
  • John M. S. Bartlett
    • 9
  1. 1.Sunnybrook Odette Cancer CentreThe University of TorontoTorontoCanada
  2. 2.University of TorontoTorontoCanada
  3. 3.Endocrine Cancer Group, Edinburgh Cancer Research CentreWestern General HospitalEdinburghUK
  4. 4.Department of Laboratory MedicineSt. Michael’s HospitalTorontoCanada
  5. 5.NCIC Clinical Trials Group (NCIC CTG) and Queen’s UniversityKingstonCanada
  6. 6.McMaster University and Hamilton Health SciencesHamiltonCanada
  7. 7.University of British ColumbiaVancouverCanada
  8. 8.British Columbia Cancer AgencyVancouverCanada
  9. 9.Ontario Institute for Cancer ResearchTorontoCanada

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