title: Targeted NGS, array-CGH, and patient-derived tumor xenografts for precision medicine in advanced breast cancer: a single-center prospective study.
abstract: BACKGROUND
  Routine feasibility and clinical impact of genomics-based tumor profiling in advanced breast cancer (aBC) remains to be determined. We conducted a pilot study to evaluate whether precision medicine could be prospectively implemented for aBC patients in a single center and to examine whether patient-derived tumor xenografts (PDX) could be obtained in this population.
  
  
  RESULTS
  Thirty-four aBC patients were included. Actionable targets were found in 28 patients (82%). A targeted therapy could be proposed to 22 patients (64%), either through a clinical trial (n=15) and/or using already registered drugs (n=21). Ten patients (29%) eventually received targeted treatment, 2 of them deriving clinical benefit. Of 22 patients subjected to mouse implantation, 10 had successful xenografting (45%), mostly in triple-negative aBC.
  
  
  METHODS
  aBC patients accessible to tumor biopsy were prospectively enrolled at the Institut Paoli-Calmettes in the BC-BIO study (ClinicalTrials.gov, NCT01521676). Genomic profiling was established by whole-genome array comparative genomic hybridization (aCGH) and targeted next-generation sequencing (NGS) of 365 candidate cancer genes. For a subset of patients, a sample of fresh tumor was orthotopically implanted in humanized cleared fat pads of NSG mice for establishing PDX.
  
  
  CONCLUSIONS
  Precision medicine can be implemented in a single center in the context of clinical practice and may allow genomic-driven treatment in approximately 30% of aBC patients. PDX may be obtained in a significant fraction of cases.
authors.affiliation: Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France.|Aix Marseille Univ, CNRS U7258, INSERM U1068, Institut Paoli-Calmettes, CRCM, Marseille, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Gonçalves
authors.affiliation: Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France.|Aix Marseille Univ, CNRS U7258, INSERM U1068, Institut Paoli-Calmettes, CRCM, Marseille, France.|Department of Molecular Oncology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: François
authors.initials: F
authors.lastname: Bertucci
authors.affiliation: Aix Marseille Univ, CNRS U7258, INSERM U1068, Institut Paoli-Calmettes, CRCM, Marseille, France.|Department of Molecular Oncology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Guille
authors.affiliation: Aix Marseille Univ, CNRS U7258, INSERM U1068, Institut Paoli-Calmettes, CRCM, Marseille, France.|Department of Molecular Oncology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Severine
authors.initials: S
authors.lastname: Garnier
authors.affiliation: Aix Marseille Univ, CNRS U7258, INSERM U1068, Institut Paoli-Calmettes, CRCM, Marseille, France.|Department of Molecular Oncology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: José
authors.initials: J
authors.lastname: Adelaide
authors.affiliation: Aix Marseille Univ, CNRS U7258, INSERM U1068, Institut Paoli-Calmettes, CRCM, Marseille, France.|Department of Molecular Oncology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Carbuccia
authors.affiliation: Aix Marseille Univ, CNRS U7258, INSERM U1068, Institut Paoli-Calmettes, CRCM, Marseille, France.|Department of Molecular Oncology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Oliver
authors.initials: O
authors.lastname: Cabaud
authors.affiliation: Aix Marseille Univ, CNRS U7258, INSERM U1068, Institut Paoli-Calmettes, CRCM, Marseille, France.|Department of Molecular Oncology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Finetti
authors.affiliation: Department of Imaging, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Brunelle
authors.affiliation: Department of Imaging, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Piana
authors.affiliation: Department of Biopathology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Tomassin-Piana
authors.affiliation: Department of Biopathology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Maria
authors.initials: M
authors.lastname: Paciencia
authors.affiliation: Department of Surgical Oncology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Lambaudie
authors.affiliation: Aix Marseille Univ, CNRS U7258, INSERM U1068, Institut Paoli-Calmettes, CRCM, Marseille, France.|Department of Oncogenetics, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Cornel
authors.initials: C
authors.lastname: Popovici
authors.affiliation: Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France.|Aix Marseille Univ, CNRS U7258, INSERM U1068, Institut Paoli-Calmettes, CRCM, Marseille, France.|Department of Molecular Oncology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Sabatier
authors.affiliation: Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Tarpin
authors.affiliation: Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Provansal
authors.affiliation: Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Extra
authors.affiliation: Aix Marseille Univ, CNRS U7258, INSERM U1068, Institut Paoli-Calmettes, CRCM, Marseille, France.|Department of Oncogenetics, Institut Paoli-Calmettes, Marseille, France.
authors.forename: François
authors.initials: F
authors.lastname: Eisinger
authors.affiliation: Aix Marseille Univ, CNRS U7258, INSERM U1068, Institut Paoli-Calmettes, CRCM, Marseille, France.|Department of Oncogenetics, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Hagay
authors.initials: H
authors.lastname: Sobol
authors.affiliation: Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France.|Aix Marseille Univ, CNRS U7258, INSERM U1068, Institut Paoli-Calmettes, CRCM, Marseille, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Viens
authors.affiliation: Aix Marseille Univ, CNRS U7258, INSERM U1068, Institut Paoli-Calmettes, CRCM, Marseille, France.|Department of Molecular Oncology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Lopez
authors.affiliation: Aix Marseille Univ, CNRS U7258, INSERM U1068, Institut Paoli-Calmettes, CRCM, Marseille, France.|Department of Molecular Oncology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Ginestier
authors.affiliation: Aix Marseille Univ, CNRS U7258, INSERM U1068, Institut Paoli-Calmettes, CRCM, Marseille, France.|Department of Molecular Oncology, Institut Paoli-Calmettes, Marseille, France.|Department of Biopathology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Charafe-Jauffret
authors.affiliation: Aix Marseille Univ, CNRS U7258, INSERM U1068, Institut Paoli-Calmettes, CRCM, Marseille, France.|Department of Molecular Oncology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Max
authors.initials: M
authors.lastname: Chaffanet
authors.affiliation: Aix Marseille Univ, CNRS U7258, INSERM U1068, Institut Paoli-Calmettes, CRCM, Marseille, France.|Department of Molecular Oncology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Birnbaum
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D055028:Comparative Genomic Hybridization / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D053263:Gene Regulatory Networks; D014644:Genetic Variation; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D051379:Mice; D008875:Middle Aged; D009368:Neoplasm Transplantation; D010865:Pilot Projects; D057285:Precision Medicine / Q000379:methods*; D011446:Prospective Studies; D017422:Sequence Analysis, DNA / Q000379:methods*
keywords: CGH; NGS; advanced breast cancer; patient-derived xenograft; precision medicine