title: Transcriptional expression of 8 genes predicts pathological response to first-line docetaxel + trastuzumab-based neoadjuvant chemotherapy.
abstract: BACKGROUND
  Overexpression of HER2 is observed in 20 to 30% of breast carcinomas. The use of trastuzumab has improved the treatment of these patients, especially when it is associated with docetaxel. To optimize the use of this treatment, it seems important to select putative complete responders before treatment administration.
  
  
  METHODS
  In this study, we analyzed by quantitative PCR the expression of 28 genes in HER2-overexpressing tumors treated with trastuzumab + docetaxel-based chemotherapy. We then correlated their expression profile with those of trastuzumab-sensitive and resistant cell lines to classify tumors as having a sensitive (pCR) or resistant (non-pCR) profile. Finally, we used public datasets from the GEO website to validate the reduced gene-expression profile obtained.
  
  
  RESULTS
  We identified an 8-gene-expression combination that predicted the response to treatment with an accuracy of 76%. Based on public microarray data, we showed that the expression profile was specific to first-line trastuzumab + docetaxel-based treatment with an accuracy of 85%.
  
  
  CONCLUSIONS
  Our results showed that by profiling the expression of 8 genes it was possible to predict the response to first-line trastuzumab + docetaxel-based chemotherapy. The use of cancer cell lines as the reference allowed a proper fit with the specificity of different tissues, such as lung or gastric cancers, which could also be eligible to concomitant HER2 inhibition by treatment with trastuzumab or tyrosine kinase inhibitors and docetaxel.
authors.affiliation: Molecular Biology Unit, Centre Georges-François Leclerc, 1, rue du Professeur Marion, Dijon, 21079 Cedex, France. schmitt.esther1704@gmail.com.
authors.forename: Esther
authors.initials: E
authors.lastname: Schmitt
authors.affiliation: Molecular Biology Unit, Centre Georges-François Leclerc, 1, rue du Professeur Marion, Dijon, 21079 Cedex, France. frederique.vegran@laposte.net.|Platform for Transfer to Cancer Biology, Centre Georges-François Leclerc, 1, rue du Professeur Marion, Dijon, 21079 Cedex, France. frederique.vegran@laposte.net.|U866 Inserm, 7, boulevard Jeanne d'Arc, Dijon, 21000, France. frederique.vegran@laposte.net.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Végran
authors.affiliation: Molecular Biology Unit, Centre Georges-François Leclerc, 1, rue du Professeur Marion, Dijon, 21079 Cedex, France. schevrier@cgfl.fr.
authors.forename: Sandy
authors.initials: S
authors.lastname: Chevrier
authors.affiliation: Pathology Unit, Centre Georges-François Leclerc, 1, rue du Professeur Marion, Dijon, 21079 Cedex, France. lburillier@cgfl.fr.
authors.forename: Laura
authors.initials: L
authors.lastname: Burillier
authors.affiliation: Molecular Biology Unit, Centre Georges-François Leclerc, 1, rue du Professeur Marion, Dijon, 21079 Cedex, France. mcadouot@cgfl.fr.
authors.forename: Muriel
authors.initials: M
authors.lastname: Cadouot
authors.affiliation: Molecular Biology Unit, Centre Georges-François Leclerc, 1, rue du Professeur Marion, Dijon, 21079 Cedex, France. slizard@cgfl.fr.
authors.forename: Sarab
authors.initials: S
authors.lastname: Lizard-Nacol
authors.affiliation: Department of Oncology, Centre Georges-François Leclerc, 1, rue du Professeur Marion, Dijon, 21079 Cedex, France. bcoudert@cgfl.fr.
authors.forename: Bruno
authors.initials: B
authors.lastname: Coudert
authors.affiliation: Department of Oncology, Centre Georges-François Leclerc, 1, rue du Professeur Marion, Dijon, 21079 Cedex, France. pfumoleau@cgfl.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Fumoleau
authors.affiliation: Pathology Unit, Centre Georges-François Leclerc, 1, rue du Professeur Marion, Dijon, 21079 Cedex, France. larnould@cgfl.fr.|Platform for Transfer to Cancer Biology, Centre Georges-François Leclerc, 1, rue du Professeur Marion, Dijon, 21079 Cedex, France. larnould@cgfl.fr.|U866 Inserm, 7, boulevard Jeanne d'Arc, Dijon, 21000, France. larnould@cgfl.fr.
authors.forename: Laurent
authors.initials: L
authors.lastname: Arnould
authors.affiliation: Molecular Biology Unit, Centre Georges-François Leclerc, 1, rue du Professeur Marion, Dijon, 21079 Cedex, France. rboidot@cgfl.fr.|Platform for Transfer to Cancer Biology, Centre Georges-François Leclerc, 1, rue du Professeur Marion, Dijon, 21079 Cedex, France. rboidot@cgfl.fr.|U866 Inserm, 7, boulevard Jeanne d'Arc, Dijon, 21000, France. rboidot@cgfl.fr.
authors.forename: Romain
authors.initials: R
authors.lastname: Boidot
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D030541:Databases, Genetic; D000077143:Docetaxel; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D043823:Taxoids / Q000008:administration & dosage*; D000068878:Trastuzumab / Q000008:administration & dosage*
chemical_list: D000077143:Docetaxel; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; C508053:ERBB2 protein, human