title: A new model of patient tumor-derived breast cancer xenografts for preclinical assays.
abstract: OBJECTIVE
  To establish a panel of human breast cancer (HBC) xenografts in immunodeficient mice suitable for pharmacologic preclinical assays.
  
  
  METHODS
  200 samples of HBCs were grafted into Swiss nude mice. Twenty-five transplantable xenografts were established (12.5%). Their characterization included histology, p53 status, genetic analysis by array comparative genomic hybridization, gene expression by Western blotting, and quantitative reverse transcription-PCR. Biological profiles of nine xenografts were compared with those of the corresponding patient's tumor. Chemosensitivities of 17 xenografts to a combination of Adriamycin and cyclophosphamide (AC), docetaxel, trastuzumab, and Degarelix were evaluated.
  
  
  RESULTS
  Almost all patient tumors established as xenografts displayed an aggressive phenotype, i.e., high-grade, triple-negative status. The histology of the xenografts recapitulated the features of the original tumors. Mutation of p53 and inactivation of Rb and PTEN proteins were found in 83%, 30%, and 42% of HBC xenografts, respectively. Two HBCx had an ERBB2 (HER2) amplification. Large variations were observed in the expression of HER family receptors and in genomic profiles. Genomic alterations were close to those of original samples in paired tumors. Three xenografts formed lung metastases. A total of 15 of the 17 HBCx (88%) responded to AC, and 8 (47%) responded to docetaxel. One ERBB2-amplified xenograft responded to trastuzumab, whereas the other did not. The drug response of HBC xenografts was concordant with that of the patient's tumor in five of seven analyzable cases.
  
  
  CONCLUSIONS
  This panel of breast cancer xenografts includes 15 triple-negative, one ER positive and 2 ERBB2 positive. This panel represents a useful preclinical tool for testing new agents and protocols and for further exploration of the biological basis of drug responses.
authors.affiliation: U612 Institut National de la Sante et de la Recherche Medicale, Pharmacologie Préclinique Antitumorale, Paris Anatomie et Cytologie Pathologique, Hôpital Trousseau, Tours, France.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Marangoni
authors.forename: Anne
authors.initials: A
authors.lastname: Vincent-Salomon
authors.forename: Nathalie
authors.initials: N
authors.lastname: Auger
authors.forename: Armelle
authors.initials: A
authors.lastname: Degeorges
authors.forename: Franck
authors.initials: F
authors.lastname: Assayag
authors.forename: Patricia
authors.initials: P
authors.lastname: de Cremoux
authors.forename: Ludmilla
authors.initials: L
authors.lastname: de Plater
authors.forename: Charlotte
authors.initials: C
authors.lastname: Guyader
authors.forename: Gonzague
authors.initials: G
authors.lastname: De Pinieux
authors.forename: Jean-Gabriel
authors.initials: JG
authors.lastname: Judde
authors.forename: Magali
authors.initials: M
authors.lastname: Rebucci
authors.forename: Carine
authors.initials: C
authors.lastname: Tran-Perennou
authors.forename: Xavier
authors.initials: X
authors.lastname: Sastre-Garau
authors.forename: Brigitte
authors.initials: B
authors.lastname: Sigal-Zafrani
authors.forename: Olivier
authors.initials: O
authors.lastname: Delattre
authors.forename: Véronique
authors.initials: V
authors.lastname: Diéras
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Poupon
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D045744:Cell Line, Tumor; D003520:Cyclophosphamide / Q000008:administration & dosage; D004195:Disease Models, Animal; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009693:Nucleic Acid Hybridization; D009842:Oligopeptides / Q000008:administration & dosage; D043823:Taxoids / Q000008:administration & dosage; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009842:Oligopeptides; D043823:Taxoids; C431566:acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; D000077143:Docetaxel; D004317:Doxorubicin; D003520:Cyclophosphamide; D000068878:Trastuzumab