title: Gene expression profile associated with response to doxorubicin-based therapy in breast cancer.
abstract: OBJECTIVE
  This study was designed to identify genes that could predict response to doxorubicin-based primary chemotherapy in breast cancer patients.
  
  
  METHODS
  Biopsy samples were obtained before primary treatment with doxorubicin and cyclophosphamide. RNA was extracted and amplified and gene expression was analyzed using cDNA microarrays.
  
  
  RESULTS
  Response to chemotherapy was evaluated in 51 patients, and based on Response Evaluation Criteria in Solid Tumors guidelines, 42 patients, who presented at least a partial response (> or =30% reduction in tumor dimension), were classified as responsive. Gene profile of samples, divided into training set (n = 38) and independent validation set (n = 13), were at first analyzed against a cDNA microarray platform containing 692 genes. Unsupervised clustering could not separate responders from nonresponders. A classifier was identified comprising EMILIN1, FAM14B, and PBEF, which however could not correctly classify samples included in the validation set. Our next step was to analyze gene profile in a more comprehensive cDNA microarray platform, containing 4,608 open reading frame expressed sequence tags. Seven samples of the initial training set (all responder patients) could not be analyzed. Unsupervised clustering could correctly group all the resistant samples as well as at least 85% of the sensitive samples. Additionally, a classifier, including PRSS11, MTSS1, and CLPTM1, could correctly distinguish 95.4% of the 44 samples analyzed, with only two misclassifications, one sensitive sample and one resistant tumor. The robustness of this classifier is 2.5 greater than the first one.
  
  
  CONCLUSIONS
  A trio of genes might potentially distinguish doxorubicin-responsive from nonresponsive tumors, but further validation by a larger number of samples is still needed.
authors.affiliation: Disciplina de Oncologia do Departamento de Radiologia da Faculdade de Medicina da Universidade de São Paulo, Brazil.
authors.forename: Maria Aparecida Azevedo Koike
authors.initials: MA
authors.lastname: Folgueira
authors.forename: Dirce Maria
authors.initials: DM
authors.lastname: Carraro
authors.forename: Helena
authors.initials: H
authors.lastname: Brentani
authors.forename: Diogo Ferreira da Costa
authors.initials: DF
authors.lastname: Patrão
authors.forename: Edson Mantovani
authors.initials: EM
authors.lastname: Barbosa
authors.forename: Mário Mourão
authors.initials: MM
authors.lastname: Netto
authors.forename: José Roberto Fígaro
authors.initials: JR
authors.lastname: Caldeira
authors.forename: Maria Lucia Hirata
authors.initials: ML
authors.lastname: Katayama
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Soares
authors.forename: Célia Tosello
authors.initials: CT
authors.lastname: Oliveira
authors.forename: Luiz Fernando Lima
authors.initials: LF
authors.lastname: Reis
authors.forename: Jane Haruko Lima
authors.initials: JH
authors.lastname: Kaiano
authors.forename: Luiz Paulo
authors.initials: LP
authors.lastname: Camargo
authors.forename: Ricardo Zorzetto Nicoliello
authors.initials: RZ
authors.lastname: Vêncio
authors.forename: Igor Moysés Longo
authors.initials: IM
authors.lastname: Snitcovsky
authors.forename: Fabiana Baroni Alves
authors.initials: FB
authors.lastname: Makdissi
authors.forename: Paulo José da Silva
authors.initials: PJ
authors.lastname: e Silva
authors.forename: João Carlos Guedes Sampaio
authors.initials: JC
authors.lastname: Góes
authors.forename: Maria Mitzi
authors.initials: MM
authors.lastname: Brentani
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016000:Cluster Analysis; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
chemical_list: D004317:Doxorubicin; D003520:Cyclophosphamide