title: Predicting Anthracycline Benefit: TOP2A and CEP17-Not Only but Also.
abstract: OBJECTIVE
  Evidence supporting the clinical utility of predictive biomarkers of anthracycline activity is weak, with a recent meta-analysis failing to provide strong evidence for either HER2 or TOP2A. Having previously shown that duplication of chromosome 17 pericentromeric alpha satellite as measured with a centromere enumeration probe (CEP17) predicted sensitivity to anthracyclines, we report here an individual patient-level pooled analysis of data from five trials comparing anthracycline-based chemotherapy with CMF (cyclophosphamide, methotrexate, and fluorouracil) as adjuvant chemotherapy for early breast cancer.
  
  
  METHODS
  Fluorescent in situ hybridization for CEP17, HER2, and TOP2A was performed in three laboratories on samples from 3,846 of 4,864 eligible patients from five trials evaluating anthracycline-containing chemotherapy versus CMF. Methodologic differences did not affect HER2-to-CEP17 ratios but necessitated different definitions for CEP17 duplication: > 1.86 observed copies per cell for BR9601, NEAT, Belgian, and DBCG89D trials and > 2.25 for the MA.5 trial.
  
  
  RESULTS
  Fluorescent in situ hybridization data were available in 89.3% (HER2), 83.9% (CEP17), and 80.6% (TOP2A) of 3,846 patient cases with available tissue. Both CEP17and TOP2A treatment-by-marker interactions remained significant in adjusted analyses for recurrence-free and overall survival, whereas HER2 did not. A combined CEP17 and TOP2A-adjusted model predicted anthracycline benefit across all five trials for both recurrence-free (hazard ratio, 0.64; 95% CI, 0.51 to 0.82; P = .001) and overall survival (hazard ratio, 0.66; 95% CI, 0.51 to 0.85; P = .005).
  
  
  CONCLUSIONS
  This prospectively planned individual-patient pooled analysis of patient cases from five adjuvant trials confirms that patients whose tumors harbor either CEP17 duplication or TOP2A aberrations, but not HER2 amplification, benefit from adjuvant anthracycline chemotherapy.
authors.affiliation: John M.S. Bartlett, Ontario Institute for Cancer Research; Frances P. O'Malley, St Michael's Hospital; Kathleen I. Pritchard, Sunnybrook Odette Cancer Centre and University of Toronto, Toronto; John M.S. Bartlett, Frances P. O'Malley, and Lois E. Shepherd, National Cancer Institute of Canada Clinical Trials Group; Lois E. Shepherd, Queen's University, Kingston, Canada; John M.S. Bartlett, Alison F. Munro, and David A. Cameron, University of Edinburgh, Edinburgh; Christopher C. McConkey, Janet A. Dunn, and Christopher J. Poole, University of Warwick, Coventry; Helena M. Earl and Carlos Caldas, University of Cambridge, Cambridge; Christopher J. Twelves, St James's University Hospital, Leeds; Daniel W. Rea, University of Birmingham, Birmingham, United Kingdom; Christine Desmedt and Denis P. Larsimont, Université Libre de Bruxelles, Brussels, Belgium; Fatima Cardoso, Champalimaud Cancer Centre, Lisbon, Portugal; Maj-Britt Jensen and Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; and Angelo Di Leo, Hospital of Prato, Prato, Italy. john.bartlett@oicr.on.ca.
authors.forename: John M S
authors.initials: JM
authors.lastname: Bartlett
authors.affiliation: John M.S. Bartlett, Ontario Institute for Cancer Research; Frances P. O'Malley, St Michael's Hospital; Kathleen I. Pritchard, Sunnybrook Odette Cancer Centre and University of Toronto, Toronto; John M.S. Bartlett, Frances P. O'Malley, and Lois E. Shepherd, National Cancer Institute of Canada Clinical Trials Group; Lois E. Shepherd, Queen's University, Kingston, Canada; John M.S. Bartlett, Alison F. Munro, and David A. Cameron, University of Edinburgh, Edinburgh; Christopher C. McConkey, Janet A. Dunn, and Christopher J. Poole, University of Warwick, Coventry; Helena M. Earl and Carlos Caldas, University of Cambridge, Cambridge; Christopher J. Twelves, St James's University Hospital, Leeds; Daniel W. Rea, University of Birmingham, Birmingham, United Kingdom; Christine Desmedt and Denis P. Larsimont, Université Libre de Bruxelles, Brussels, Belgium; Fatima Cardoso, Champalimaud Cancer Centre, Lisbon, Portugal; Maj-Britt Jensen and Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; and Angelo Di Leo, Hospital of Prato, Prato, Italy.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: McConkey
authors.affiliation: John M.S. Bartlett, Ontario Institute for Cancer Research; Frances P. O'Malley, St Michael's Hospital; Kathleen I. Pritchard, Sunnybrook Odette Cancer Centre and University of Toronto, Toronto; John M.S. Bartlett, Frances P. O'Malley, and Lois E. Shepherd, National Cancer Institute of Canada Clinical Trials Group; Lois E. Shepherd, Queen's University, Kingston, Canada; John M.S. Bartlett, Alison F. Munro, and David A. Cameron, University of Edinburgh, Edinburgh; Christopher C. McConkey, Janet A. Dunn, and Christopher J. Poole, University of Warwick, Coventry; Helena M. Earl and Carlos Caldas, University of Cambridge, Cambridge; Christopher J. Twelves, St James's University Hospital, Leeds; Daniel W. Rea, University of Birmingham, Birmingham, United Kingdom; Christine Desmedt and Denis P. Larsimont, Université Libre de Bruxelles, Brussels, Belgium; Fatima Cardoso, Champalimaud Cancer Centre, Lisbon, Portugal; Maj-Britt Jensen and Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; and Angelo Di Leo, Hospital of Prato, Prato, Italy.
authors.forename: Alison F
authors.initials: AF
authors.lastname: Munro
authors.affiliation: John M.S. Bartlett, Ontario Institute for Cancer Research; Frances P. O'Malley, St Michael's Hospital; Kathleen I. Pritchard, Sunnybrook Odette Cancer Centre and University of Toronto, Toronto; John M.S. Bartlett, Frances P. O'Malley, and Lois E. Shepherd, National Cancer Institute of Canada Clinical Trials Group; Lois E. Shepherd, Queen's University, Kingston, Canada; John M.S. Bartlett, Alison F. Munro, and David A. Cameron, University of Edinburgh, Edinburgh; Christopher C. McConkey, Janet A. Dunn, and Christopher J. Poole, University of Warwick, Coventry; Helena M. Earl and Carlos Caldas, University of Cambridge, Cambridge; Christopher J. Twelves, St James's University Hospital, Leeds; Daniel W. Rea, University of Birmingham, Birmingham, United Kingdom; Christine Desmedt and Denis P. Larsimont, Université Libre de Bruxelles, Brussels, Belgium; Fatima Cardoso, Champalimaud Cancer Centre, Lisbon, Portugal; Maj-Britt Jensen and Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; and Angelo Di Leo, Hospital of Prato, Prato, Italy.
authors.forename: Christine
authors.initials: C
authors.lastname: Desmedt
authors.affiliation: John M.S. Bartlett, Ontario Institute for Cancer Research; Frances P. O'Malley, St Michael's Hospital; Kathleen I. Pritchard, Sunnybrook Odette Cancer Centre and University of Toronto, Toronto; John M.S. Bartlett, Frances P. O'Malley, and Lois E. Shepherd, National Cancer Institute of Canada Clinical Trials Group; Lois E. Shepherd, Queen's University, Kingston, Canada; John M.S. Bartlett, Alison F. Munro, and David A. Cameron, University of Edinburgh, Edinburgh; Christopher C. McConkey, Janet A. Dunn, and Christopher J. Poole, University of Warwick, Coventry; Helena M. Earl and Carlos Caldas, University of Cambridge, Cambridge; Christopher J. Twelves, St James's University Hospital, Leeds; Daniel W. Rea, University of Birmingham, Birmingham, United Kingdom; Christine Desmedt and Denis P. Larsimont, Université Libre de Bruxelles, Brussels, Belgium; Fatima Cardoso, Champalimaud Cancer Centre, Lisbon, Portugal; Maj-Britt Jensen and Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; and Angelo Di Leo, Hospital of Prato, Prato, Italy.
authors.forename: Janet A
authors.initials: JA
authors.lastname: Dunn
authors.affiliation: John M.S. Bartlett, Ontario Institute for Cancer Research; Frances P. O'Malley, St Michael's Hospital; Kathleen I. Pritchard, Sunnybrook Odette Cancer Centre and University of Toronto, Toronto; John M.S. Bartlett, Frances P. O'Malley, and Lois E. Shepherd, National Cancer Institute of Canada Clinical Trials Group; Lois E. Shepherd, Queen's University, Kingston, Canada; John M.S. Bartlett, Alison F. Munro, and David A. Cameron, University of Edinburgh, Edinburgh; Christopher C. McConkey, Janet A. Dunn, and Christopher J. Poole, University of Warwick, Coventry; Helena M. Earl and Carlos Caldas, University of Cambridge, Cambridge; Christopher J. Twelves, St James's University Hospital, Leeds; Daniel W. Rea, University of Birmingham, Birmingham, United Kingdom; Christine Desmedt and Denis P. Larsimont, Université Libre de Bruxelles, Brussels, Belgium; Fatima Cardoso, Champalimaud Cancer Centre, Lisbon, Portugal; Maj-Britt Jensen and Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; and Angelo Di Leo, Hospital of Prato, Prato, Italy.
authors.forename: Denis P
authors.initials: DP
authors.lastname: Larsimont
authors.affiliation: John M.S. Bartlett, Ontario Institute for Cancer Research; Frances P. O'Malley, St Michael's Hospital; Kathleen I. Pritchard, Sunnybrook Odette Cancer Centre and University of Toronto, Toronto; John M.S. Bartlett, Frances P. O'Malley, and Lois E. Shepherd, National Cancer Institute of Canada Clinical Trials Group; Lois E. Shepherd, Queen's University, Kingston, Canada; John M.S. Bartlett, Alison F. Munro, and David A. Cameron, University of Edinburgh, Edinburgh; Christopher C. McConkey, Janet A. Dunn, and Christopher J. Poole, University of Warwick, Coventry; Helena M. Earl and Carlos Caldas, University of Cambridge, Cambridge; Christopher J. Twelves, St James's University Hospital, Leeds; Daniel W. Rea, University of Birmingham, Birmingham, United Kingdom; Christine Desmedt and Denis P. Larsimont, Université Libre de Bruxelles, Brussels, Belgium; Fatima Cardoso, Champalimaud Cancer Centre, Lisbon, Portugal; Maj-Britt Jensen and Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; and Angelo Di Leo, Hospital of Prato, Prato, Italy.
authors.forename: Frances P
authors.initials: FP
authors.lastname: O'Malley
authors.affiliation: John M.S. Bartlett, Ontario Institute for Cancer Research; Frances P. O'Malley, St Michael's Hospital; Kathleen I. Pritchard, Sunnybrook Odette Cancer Centre and University of Toronto, Toronto; John M.S. Bartlett, Frances P. O'Malley, and Lois E. Shepherd, National Cancer Institute of Canada Clinical Trials Group; Lois E. Shepherd, Queen's University, Kingston, Canada; John M.S. Bartlett, Alison F. Munro, and David A. Cameron, University of Edinburgh, Edinburgh; Christopher C. McConkey, Janet A. Dunn, and Christopher J. Poole, University of Warwick, Coventry; Helena M. Earl and Carlos Caldas, University of Cambridge, Cambridge; Christopher J. Twelves, St James's University Hospital, Leeds; Daniel W. Rea, University of Birmingham, Birmingham, United Kingdom; Christine Desmedt and Denis P. Larsimont, Université Libre de Bruxelles, Brussels, Belgium; Fatima Cardoso, Champalimaud Cancer Centre, Lisbon, Portugal; Maj-Britt Jensen and Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; and Angelo Di Leo, Hospital of Prato, Prato, Italy.
authors.forename: David A
authors.initials: DA
authors.lastname: Cameron
authors.affiliation: John M.S. Bartlett, Ontario Institute for Cancer Research; Frances P. O'Malley, St Michael's Hospital; Kathleen I. Pritchard, Sunnybrook Odette Cancer Centre and University of Toronto, Toronto; John M.S. Bartlett, Frances P. O'Malley, and Lois E. Shepherd, National Cancer Institute of Canada Clinical Trials Group; Lois E. Shepherd, Queen's University, Kingston, Canada; John M.S. Bartlett, Alison F. Munro, and David A. Cameron, University of Edinburgh, Edinburgh; Christopher C. McConkey, Janet A. Dunn, and Christopher J. Poole, University of Warwick, Coventry; Helena M. Earl and Carlos Caldas, University of Cambridge, Cambridge; Christopher J. Twelves, St James's University Hospital, Leeds; Daniel W. Rea, University of Birmingham, Birmingham, United Kingdom; Christine Desmedt and Denis P. Larsimont, Université Libre de Bruxelles, Brussels, Belgium; Fatima Cardoso, Champalimaud Cancer Centre, Lisbon, Portugal; Maj-Britt Jensen and Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; and Angelo Di Leo, Hospital of Prato, Prato, Italy.
authors.forename: Helena M
authors.initials: HM
authors.lastname: Earl
authors.affiliation: John M.S. Bartlett, Ontario Institute for Cancer Research; Frances P. O'Malley, St Michael's Hospital; Kathleen I. Pritchard, Sunnybrook Odette Cancer Centre and University of Toronto, Toronto; John M.S. Bartlett, Frances P. O'Malley, and Lois E. Shepherd, National Cancer Institute of Canada Clinical Trials Group; Lois E. Shepherd, Queen's University, Kingston, Canada; John M.S. Bartlett, Alison F. Munro, and David A. Cameron, University of Edinburgh, Edinburgh; Christopher C. McConkey, Janet A. Dunn, and Christopher J. Poole, University of Warwick, Coventry; Helena M. Earl and Carlos Caldas, University of Cambridge, Cambridge; Christopher J. Twelves, St James's University Hospital, Leeds; Daniel W. Rea, University of Birmingham, Birmingham, United Kingdom; Christine Desmedt and Denis P. Larsimont, Université Libre de Bruxelles, Brussels, Belgium; Fatima Cardoso, Champalimaud Cancer Centre, Lisbon, Portugal; Maj-Britt Jensen and Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; and Angelo Di Leo, Hospital of Prato, Prato, Italy.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Poole
authors.affiliation: John M.S. Bartlett, Ontario Institute for Cancer Research; Frances P. O'Malley, St Michael's Hospital; Kathleen I. Pritchard, Sunnybrook Odette Cancer Centre and University of Toronto, Toronto; John M.S. Bartlett, Frances P. O'Malley, and Lois E. Shepherd, National Cancer Institute of Canada Clinical Trials Group; Lois E. Shepherd, Queen's University, Kingston, Canada; John M.S. Bartlett, Alison F. Munro, and David A. Cameron, University of Edinburgh, Edinburgh; Christopher C. McConkey, Janet A. Dunn, and Christopher J. Poole, University of Warwick, Coventry; Helena M. Earl and Carlos Caldas, University of Cambridge, Cambridge; Christopher J. Twelves, St James's University Hospital, Leeds; Daniel W. Rea, University of Birmingham, Birmingham, United Kingdom; Christine Desmedt and Denis P. Larsimont, Université Libre de Bruxelles, Brussels, Belgium; Fatima Cardoso, Champalimaud Cancer Centre, Lisbon, Portugal; Maj-Britt Jensen and Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; and Angelo Di Leo, Hospital of Prato, Prato, Italy.
authors.forename: Lois E
authors.initials: LE
authors.lastname: Shepherd
authors.affiliation: John M.S. Bartlett, Ontario Institute for Cancer Research; Frances P. O'Malley, St Michael's Hospital; Kathleen I. Pritchard, Sunnybrook Odette Cancer Centre and University of Toronto, Toronto; John M.S. Bartlett, Frances P. O'Malley, and Lois E. Shepherd, National Cancer Institute of Canada Clinical Trials Group; Lois E. Shepherd, Queen's University, Kingston, Canada; John M.S. Bartlett, Alison F. Munro, and David A. Cameron, University of Edinburgh, Edinburgh; Christopher C. McConkey, Janet A. Dunn, and Christopher J. Poole, University of Warwick, Coventry; Helena M. Earl and Carlos Caldas, University of Cambridge, Cambridge; Christopher J. Twelves, St James's University Hospital, Leeds; Daniel W. Rea, University of Birmingham, Birmingham, United Kingdom; Christine Desmedt and Denis P. Larsimont, Université Libre de Bruxelles, Brussels, Belgium; Fatima Cardoso, Champalimaud Cancer Centre, Lisbon, Portugal; Maj-Britt Jensen and Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; and Angelo Di Leo, Hospital of Prato, Prato, Italy.
authors.forename: Fatima
authors.initials: F
authors.lastname: Cardoso
authors.affiliation: John M.S. Bartlett, Ontario Institute for Cancer Research; Frances P. O'Malley, St Michael's Hospital; Kathleen I. Pritchard, Sunnybrook Odette Cancer Centre and University of Toronto, Toronto; John M.S. Bartlett, Frances P. O'Malley, and Lois E. Shepherd, National Cancer Institute of Canada Clinical Trials Group; Lois E. Shepherd, Queen's University, Kingston, Canada; John M.S. Bartlett, Alison F. Munro, and David A. Cameron, University of Edinburgh, Edinburgh; Christopher C. McConkey, Janet A. Dunn, and Christopher J. Poole, University of Warwick, Coventry; Helena M. Earl and Carlos Caldas, University of Cambridge, Cambridge; Christopher J. Twelves, St James's University Hospital, Leeds; Daniel W. Rea, University of Birmingham, Birmingham, United Kingdom; Christine Desmedt and Denis P. Larsimont, Université Libre de Bruxelles, Brussels, Belgium; Fatima Cardoso, Champalimaud Cancer Centre, Lisbon, Portugal; Maj-Britt Jensen and Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; and Angelo Di Leo, Hospital of Prato, Prato, Italy.
authors.forename: Maj-Britt
authors.initials: MB
authors.lastname: Jensen
authors.affiliation: John M.S. Bartlett, Ontario Institute for Cancer Research; Frances P. O'Malley, St Michael's Hospital; Kathleen I. Pritchard, Sunnybrook Odette Cancer Centre and University of Toronto, Toronto; John M.S. Bartlett, Frances P. O'Malley, and Lois E. Shepherd, National Cancer Institute of Canada Clinical Trials Group; Lois E. Shepherd, Queen's University, Kingston, Canada; John M.S. Bartlett, Alison F. Munro, and David A. Cameron, University of Edinburgh, Edinburgh; Christopher C. McConkey, Janet A. Dunn, and Christopher J. Poole, University of Warwick, Coventry; Helena M. Earl and Carlos Caldas, University of Cambridge, Cambridge; Christopher J. Twelves, St James's University Hospital, Leeds; Daniel W. Rea, University of Birmingham, Birmingham, United Kingdom; Christine Desmedt and Denis P. Larsimont, Université Libre de Bruxelles, Brussels, Belgium; Fatima Cardoso, Champalimaud Cancer Centre, Lisbon, Portugal; Maj-Britt Jensen and Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; and Angelo Di Leo, Hospital of Prato, Prato, Italy.
authors.forename: Carlos
authors.initials: C
authors.lastname: Caldas
authors.affiliation: John M.S. Bartlett, Ontario Institute for Cancer Research; Frances P. O'Malley, St Michael's Hospital; Kathleen I. Pritchard, Sunnybrook Odette Cancer Centre and University of Toronto, Toronto; John M.S. Bartlett, Frances P. O'Malley, and Lois E. Shepherd, National Cancer Institute of Canada Clinical Trials Group; Lois E. Shepherd, Queen's University, Kingston, Canada; John M.S. Bartlett, Alison F. Munro, and David A. Cameron, University of Edinburgh, Edinburgh; Christopher C. McConkey, Janet A. Dunn, and Christopher J. Poole, University of Warwick, Coventry; Helena M. Earl and Carlos Caldas, University of Cambridge, Cambridge; Christopher J. Twelves, St James's University Hospital, Leeds; Daniel W. Rea, University of Birmingham, Birmingham, United Kingdom; Christine Desmedt and Denis P. Larsimont, Université Libre de Bruxelles, Brussels, Belgium; Fatima Cardoso, Champalimaud Cancer Centre, Lisbon, Portugal; Maj-Britt Jensen and Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; and Angelo Di Leo, Hospital of Prato, Prato, Italy.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Twelves
authors.affiliation: John M.S. Bartlett, Ontario Institute for Cancer Research; Frances P. O'Malley, St Michael's Hospital; Kathleen I. Pritchard, Sunnybrook Odette Cancer Centre and University of Toronto, Toronto; John M.S. Bartlett, Frances P. O'Malley, and Lois E. Shepherd, National Cancer Institute of Canada Clinical Trials Group; Lois E. Shepherd, Queen's University, Kingston, Canada; John M.S. Bartlett, Alison F. Munro, and David A. Cameron, University of Edinburgh, Edinburgh; Christopher C. McConkey, Janet A. Dunn, and Christopher J. Poole, University of Warwick, Coventry; Helena M. Earl and Carlos Caldas, University of Cambridge, Cambridge; Christopher J. Twelves, St James's University Hospital, Leeds; Daniel W. Rea, University of Birmingham, Birmingham, United Kingdom; Christine Desmedt and Denis P. Larsimont, Université Libre de Bruxelles, Brussels, Belgium; Fatima Cardoso, Champalimaud Cancer Centre, Lisbon, Portugal; Maj-Britt Jensen and Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; and Angelo Di Leo, Hospital of Prato, Prato, Italy.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Rea
authors.affiliation: John M.S. Bartlett, Ontario Institute for Cancer Research; Frances P. O'Malley, St Michael's Hospital; Kathleen I. Pritchard, Sunnybrook Odette Cancer Centre and University of Toronto, Toronto; John M.S. Bartlett, Frances P. O'Malley, and Lois E. Shepherd, National Cancer Institute of Canada Clinical Trials Group; Lois E. Shepherd, Queen's University, Kingston, Canada; John M.S. Bartlett, Alison F. Munro, and David A. Cameron, University of Edinburgh, Edinburgh; Christopher C. McConkey, Janet A. Dunn, and Christopher J. Poole, University of Warwick, Coventry; Helena M. Earl and Carlos Caldas, University of Cambridge, Cambridge; Christopher J. Twelves, St James's University Hospital, Leeds; Daniel W. Rea, University of Birmingham, Birmingham, United Kingdom; Christine Desmedt and Denis P. Larsimont, Université Libre de Bruxelles, Brussels, Belgium; Fatima Cardoso, Champalimaud Cancer Centre, Lisbon, Portugal; Maj-Britt Jensen and Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; and Angelo Di Leo, Hospital of Prato, Prato, Italy.
authors.forename: Bent
authors.initials: B
authors.lastname: Ejlertsen
authors.affiliation: John M.S. Bartlett, Ontario Institute for Cancer Research; Frances P. O'Malley, St Michael's Hospital; Kathleen I. Pritchard, Sunnybrook Odette Cancer Centre and University of Toronto, Toronto; John M.S. Bartlett, Frances P. O'Malley, and Lois E. Shepherd, National Cancer Institute of Canada Clinical Trials Group; Lois E. Shepherd, Queen's University, Kingston, Canada; John M.S. Bartlett, Alison F. Munro, and David A. Cameron, University of Edinburgh, Edinburgh; Christopher C. McConkey, Janet A. Dunn, and Christopher J. Poole, University of Warwick, Coventry; Helena M. Earl and Carlos Caldas, University of Cambridge, Cambridge; Christopher J. Twelves, St James's University Hospital, Leeds; Daniel W. Rea, University of Birmingham, Birmingham, United Kingdom; Christine Desmedt and Denis P. Larsimont, Université Libre de Bruxelles, Brussels, Belgium; Fatima Cardoso, Champalimaud Cancer Centre, Lisbon, Portugal; Maj-Britt Jensen and Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; and Angelo Di Leo, Hospital of Prato, Prato, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Di Leo
authors.affiliation: John M.S. Bartlett, Ontario Institute for Cancer Research; Frances P. O'Malley, St Michael's Hospital; Kathleen I. Pritchard, Sunnybrook Odette Cancer Centre and University of Toronto, Toronto; John M.S. Bartlett, Frances P. O'Malley, and Lois E. Shepherd, National Cancer Institute of Canada Clinical Trials Group; Lois E. Shepherd, Queen's University, Kingston, Canada; John M.S. Bartlett, Alison F. Munro, and David A. Cameron, University of Edinburgh, Edinburgh; Christopher C. McConkey, Janet A. Dunn, and Christopher J. Poole, University of Warwick, Coventry; Helena M. Earl and Carlos Caldas, University of Cambridge, Cambridge; Christopher J. Twelves, St James's University Hospital, Leeds; Daniel W. Rea, University of Birmingham, Birmingham, United Kingdom; Christine Desmedt and Denis P. Larsimont, Université Libre de Bruxelles, Brussels, Belgium; Fatima Cardoso, Champalimaud Cancer Centre, Lisbon, Portugal; Maj-Britt Jensen and Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; and Angelo Di Leo, Hospital of Prato, Prato, Italy.
authors.forename: Kathleen I
authors.initials: KI
authors.lastname: Pritchard
mesh_terms: D018943:Anthracyclines / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000235:genetics*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D002503:Centromere / Q000737:chemistry*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D017326:Clinical Trials, Phase III as Topic; D003520:Cyclophosphamide / Q000627:therapeutic use; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D018572:Disease-Free Survival; D005456:Fluorescent Dyes / Q000737:chemistry*; D005472:Fluorouracil / Q000627:therapeutic use; D005819:Genetic Markers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008727:Methotrexate / Q000627:therapeutic use; D009364:Neoplasm Recurrence, Local; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D000075223:Poly-ADP-Ribose Binding Proteins; D011379:Prognosis; D016016:Proportional Hazards Models; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D005456:Fluorescent Dyes; D005819:Genetic Markers; D000075223:Poly-ADP-Ribose Binding Proteins; D003520:Cyclophosphamide; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human; D005472:Fluorouracil; D008727:Methotrexate