title: Clinical and genomic analysis of a randomised phase II study evaluating anastrozole and fulvestrant in postmenopausal patients treated for large operable or locally advanced hormone-receptor-positive breast cancer.
abstract: BACKGROUND
  The aim of this study was to assess the efficacy of neoadjuvant anastrozole and fulvestrant treatment of large operable or locally advanced hormone-receptor-positive breast cancer not eligible for initial breast-conserving surgery, and to identify genomic changes occurring after treatment.
  
  
  METHODS
  One hundred and twenty post-menopausal patients were randomised to receive 1 mg anastrozole (61 patients) or 500 mg fulvestrant (59 patients) for 6 months. Genomic DNA copy number profiles were generated for a subgroup of 20 patients before and after treatment.
  
  
  RESULTS
  A total of 108 patients were evaluable for efficacy and 118 for toxicity. The objective response rate determined by clinical palpation was 58.9% (95% CI=45.0-71.9) in the anastrozole arm and 53.8% (95% CI=39.5-67.8) in the fulvestrant arm. The breast-conserving surgery rate was 58.9% (95% CI=45.0-71.9) in the anastrozole arm and 50.0% (95% CI=35.8-64.2) in the fulvestrant arm. Pathological responses >50% occurred in 24 patients (42.9%) in the anastrozole arm and 13 (25.0%) in the fulvestrant arm. The Ki-67 score fell after treatment but there was no significant difference between the reduction in the two arms (anastrozole 16.7% (95% CI=13.3-21.0) before, 3.2% (95% CI=1.9-5.5) after, n=43; fulvestrant 17.1% (95%CI=13.1-22.5) before, 3.2% (95% CI=1.8-5.7) after, n=38) or between the reduction in Ki-67 in clinical responders and non-responders. Genomic analysis appeared to show a reduction of clonal diversity following treatment with selection of some clones with simpler copy number profiles.
  
  
  CONCLUSIONS
  Both anastrozole and fulvestrant were effective and well-tolerated, enabling breast-conserving surgery in over 50% of patients. Clonal changes consistent with clonal selection by the treatment were seen in a subgroup of patients.
authors.affiliation: Institut Bergonié Comprehensive Cancer Centre, 229 Cours de l'Argonne, F-33000 Bordeaux, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Quenel-Tueux
authors.affiliation: Institut Bergonié Comprehensive Cancer Centre, 229 Cours de l'Argonne, F-33000 Bordeaux, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Debled
authors.affiliation: 1] Institut Bergonié Comprehensive Cancer Centre, 229 Cours de l'Argonne, F-33000 Bordeaux, France [2] INSERM U916, 229 Cours de l'Argonne, F-33000 Bordeaux, France [3] University Bordeaux, 16 Avenue Léon Duguit, F-33608 Pessac, France [4] Bordeaux Bioinformatics Centre, University Bordeaux, 146, rue Léo Saignat, F-33076 Bordeaux, France [5] CNRS UMR5800, Bordeaux Computer Science Lab, 351 Cours de la Libération, F-33405 Talence, France.
authors.forename: Justine
authors.initials: J
authors.lastname: Rudewicz
authors.affiliation: 1] Institut Bergonié Comprehensive Cancer Centre, 229 Cours de l'Argonne, F-33000 Bordeaux, France [2] INSERM U916, 229 Cours de l'Argonne, F-33000 Bordeaux, France [3] University Bordeaux, 16 Avenue Léon Duguit, F-33608 Pessac, France.
authors.forename: Gaetan
authors.initials: G
authors.lastname: MacGrogan
authors.affiliation: 1] Inserm Clinical Investigation Centre CIC1401, Epidemiological Unit, 229 Cours de l'Argonne, Bordeaux 33076, France [2] Clinical and Epidemiological Research Unit, Institut Bergonie, 229 Cours de l'Argonne, Bordeaux 33076, France.
authors.forename: Marina
authors.initials: M
authors.lastname: Pulido
authors.affiliation: Institut Bergonié Comprehensive Cancer Centre, 229 Cours de l'Argonne, F-33000 Bordeaux, France.
authors.forename: Louis
authors.initials: L
authors.lastname: Mauriac
authors.affiliation: Institut Claudius Regaud, IUCT-Oncopole Toulouse, 1 Avenue Irène Joliot-Curie, F-31059 Toulouse, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Dalenc
authors.affiliation: CLCC Lyon, 28 Promenade Léa et Napoléon Bullukian, F-69008 Lyon, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bachelot
authors.affiliation: Institut Bergonié Comprehensive Cancer Centre, 229 Cours de l'Argonne, F-33000 Bordeaux, France.
authors.forename: Barbara
authors.initials: B
authors.lastname: Lortal
authors.affiliation: Institut Bergonié Comprehensive Cancer Centre, 229 Cours de l'Argonne, F-33000 Bordeaux, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Breton-Callu
authors.affiliation: Institut Bergonié Comprehensive Cancer Centre, 229 Cours de l'Argonne, F-33000 Bordeaux, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Madranges
authors.affiliation: Institut Bergonié Comprehensive Cancer Centre, 229 Cours de l'Argonne, F-33000 Bordeaux, France.
authors.forename: Christine Tunon
authors.initials: CT
authors.lastname: de Lara
authors.affiliation: Institut Bergonié Comprehensive Cancer Centre, 229 Cours de l'Argonne, F-33000 Bordeaux, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Fournier
authors.affiliation: 1] Institut Bergonié Comprehensive Cancer Centre, 229 Cours de l'Argonne, F-33000 Bordeaux, France [2] INSERM U916, 229 Cours de l'Argonne, F-33000 Bordeaux, France [3] University Bordeaux, 16 Avenue Léon Duguit, F-33608 Pessac, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Bonnefoi
authors.affiliation: Bordeaux Bioinformatics Centre, University Bordeaux, 146, rue Léo Saignat, F-33076 Bordeaux, France.
authors.forename: Hayssam
authors.initials: H
authors.lastname: Soueidan
authors.affiliation: 1] University Bordeaux, 16 Avenue Léon Duguit, F-33608 Pessac, France [2] Bordeaux Bioinformatics Centre, University Bordeaux, 146, rue Léo Saignat, F-33076 Bordeaux, France [3] CNRS UMR5800, Bordeaux Computer Science Lab, 351 Cours de la Libération, F-33405 Talence, France.
authors.forename: Macha
authors.initials: M
authors.lastname: Nikolski
authors.affiliation: 1] Institut Bergonié Comprehensive Cancer Centre, 229 Cours de l'Argonne, F-33000 Bordeaux, France [2] INSERM U916, 229 Cours de l'Argonne, F-33000 Bordeaux, France [3] University Bordeaux, 16 Avenue Léon Duguit, F-33608 Pessac, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Gros
authors.affiliation: Leeds Institute of Cancer and Pathology, University of Leeds, Beckett Street, Leeds LS9 7TF, UK.
authors.forename: Catherine
authors.initials: C
authors.lastname: Daly
authors.affiliation: Leeds Institute of Cancer and Pathology, University of Leeds, Beckett Street, Leeds LS9 7TF, UK.
authors.forename: Henry
authors.initials: H
authors.lastname: Wood
authors.affiliation: Leeds Institute of Cancer and Pathology, University of Leeds, Beckett Street, Leeds LS9 7TF, UK.
authors.forename: Pamela
authors.initials: P
authors.lastname: Rabbitts
authors.affiliation: 1] Institut Bergonié Comprehensive Cancer Centre, 229 Cours de l'Argonne, F-33000 Bordeaux, France [2] INSERM U916, 229 Cours de l'Argonne, F-33000 Bordeaux, France [3] University Bordeaux, 16 Avenue Léon Duguit, F-33608 Pessac, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Iggo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use*; D017698:Postmenopause / Q000187:drug effects*; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D009570:Nitriles; D014230:Triazoles; D000077267:Fulvestrant; D000077384:Anastrozole; D004958:Estradiol