title: Comparative genomic hybridisation array and DNA sequencing to direct treatment of metastatic breast cancer: a multicentre, prospective trial (SAFIR01/UNICANCER).
abstract: BACKGROUND
  Breast cancer is characterised by genomic alterations. We did a multicentre molecular screening study to identify abnormalities in individual patients with the aim of providing targeted therapy matched to individuals' genomic alterations.
  
  
  METHODS
  From June 16, 2011, to July 30, 2012, we recruited patients who had breast cancer with a metastasis accessible for biopsy in 18 centres in France. Comparative genomic hybridisation (CGH) array and Sanger sequencing on PIK3CA (exon 10 and 21) and AKT1 (exon 4) were used to assess metastatic biopsy samples in five centres. Therapeutic targets were decided on the basis of identified genomic alterations. The primary objective was to include 30% of patients in clinical trials testing a targeted therapy and, therefore, the primary outcome was the proportion of patients to whom a targeted therapy could be offered. For the primary endpoint, the analyses were done on the overall population registered for the trial. This trial is registered with ClinicalTrials.gov, number NCT01414933.
  
  
  RESULTS
  423 patients were included, and biopsy samples were obtained from 407 (metastatic breast cancer was not found in four). CGH array and Sanger sequencing were feasible in 283 (67%) and 297 (70%) patients, respectively. A targetable genomic alteration was identified in 195 (46%) patients, most frequently in PIK3CA (74 [25%] of 297 identified genomic alterations), CCND1 (53 [19%]), and FGFR1 (36 [13%]). 117 (39%) of 297 patients with genomic tests available presented with rare genomic alterations (defined as occurring in less than 5% of the general population), including AKT1 mutations, and EGFR, MDM2, FGFR2, AKT2, IGF1R, and MET high-level amplifications. Therapy could be personalised in 55 (13%) of 423 patients. Of the 43 patients who were assessable and received targeted therapy, four (9%) had an objective response, and nine others (21%) had stable disease for more than 16 weeks. Serious (grade 3 or higher) adverse events related to biopsy were reported in four (1%) of enrolled patients, including pneumothorax (grade 3, one patient), pain (grade 3, one patient), haematoma (grade 3, one patient), and haemorrhagic shock (grade 3, one patient).
  
  
  CONCLUSIONS
  Personalisation of medicine for metastatic breast cancer is feasible, including for rare genomic alterations.
  
  
  BACKGROUND
  French National Cancer Institute, Breast Cancer Research Foundation, Odyssea, Operation Parrains Chercheurs.
authors: Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France; INSERM Unit U981, Institut Gustave Roussy, Villejuif, France; Université Paris Sud, le Kremlin Bicêtre, France. Electronic address: fabrice.andre@gustaveroussy.fr.
authors: Fabrice
authors: F
authors: André
authors: Departement de Cancerologie Medicale, Université Lyon 1, Centre Léon Bérard, Lyon, France.
authors: Thomas
authors: T
authors: Bachelot
authors: INSERM Unit U981, Institut Gustave Roussy, Villejuif, France.
authors: Frederic
authors: F
authors: Commo
authors: Institut de Cancérologie de l'Ouest/René Gauducheau, Nantes Saint Herblain, France.
authors: Mario
authors: M
authors: Campone
authors: Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France; INSERM Unit U981, Institut Gustave Roussy, Villejuif, France.
authors: Monica
authors: M
authors: Arnedos
authors: Department of Medical Oncology, Institut Curie, Paris, France.
authors: Véronique
authors: V
authors: Dieras
authors: Institut Claudius Regaud, Department of Pathology, Toulouse, France.
authors: Magali
authors: M
authors: Lacroix-Triki
authors: Department of Translational Research, Institut Gustave Roussy, Villejuif, France.
authors: Ludovic
authors: L
authors: Lacroix
authors: Centre Léon Bérard, Lyon, France; Université Lyon 1, Lyon, France; ProfileXpert, SFR Lyon-Est, Lyon, France.
authors: Pascale
authors: P
authors: Cohen
authors: Department of Translational Research, Institut Curie, Paris, France.
authors: David
authors: D
authors: Gentien
authors: Molecular Oncology Department, Institut Paoli Calmettes, Marseille, France.
authors: Jose
authors: J
authors: Adélaide
authors: Department of Medical Oncology, Institut Claudius Regaud, Toulouse, France.
authors: Florence
authors: F
authors: Dalenc
authors: Department of Medical Oncology, Institut Paoli Calmettes, Marseille, France.
authors: Anthony
authors: A
authors: Goncalves
authors: Department of Medical Oncology, Centre François Baclesse, Caen, France.
authors: Christelle
authors: C
authors: Levy
authors: Department of Medical Oncology, Centre Antoine Lacassagne, Nice, France.
authors: Jean-Marc
authors: JM
authors: Ferrero
authors: Department of Medical Oncology, Centre Oscar Lambret, Lille, France.
authors: Jacques
authors: J
authors: Bonneterre
authors: Department of Medical Oncology, Centre Eugène Marquis, Rennes, France.
authors: Claudia
authors: C
authors: Lefeuvre
authors: Research and Development Unit, UNICANCER, Paris, France.
authors: Marta
authors: M
authors: Jimenez
authors: Department of Biostatistics, Institut Claudius Regaud, Toulouse, France.
authors: Thomas
authors: T
authors: Filleron
authors: Department of Medical Oncology, Institut Bergonié, Université de Bordeaux, INSERM U916, Bordeaux, France.
authors: Hervé
authors: H
authors: Bonnefoi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D055028:Comparative Genomic Hybridization / Q000379:methods*; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011446:Prospective Studies; D017422:Sequence Analysis, DNA / Q000379:methods*