title: FOXP3 expression in cancer cells and anthracyclines efficacy in patients with primary breast cancer treated with adjuvant chemotherapy in the phase III UNICANCER-PACS 01 trial.
abstract: BACKGROUND
  Predictive markers of response to chemotherapy are lacking in breast cancer patients. Forkhead Box Protein 3 (FOXP3) is an anti-oncogene whose absence in cancer cells could confer resistance to DNA damaging agent. So we made the hypothesis that FOXP3 expression predicts the response to anthracyclines in breast cancer patients and that adjuvant chemotherapy adding taxanes to anthracyclines confers an overall survival (OS) benefit over anthracyclines alone, in patients with FOXP3-negative tumors.
  
  
  METHODS
  Expression of FOXP3 in cancer cells was evaluated by immunohistochemistry in tumor samples from 1097 patients who participated in the PACS01 randomized trial that evaluated in adjuvant setting the adjunction of docetaxel (Taxotere) to anthracyclines in patients with localized breast cancer. Kaplan-Meier analysis and Cox regression model were used to assess OS according to the presence or absence of FOXP3 expression in tumor cells.
  
  
  RESULTS
  Four hundred and five tumors were found to express FOXP3 (37%). FOXP3 expression in breast cancer cells was associated with better OS (P = 0.003). Uni- and multivariate survival analyses according to treatment arm revealed that FOXP3 expression in breast cancer cells is independently associated with improved OS in patients treated with anthracycline-based adjuvant chemotherapy, but not in patients treated with sequential anthracycline-taxane. Moreover, in vitro experiments showed that FOXP3 induction in breast cancer cell lines using histone deacetylase inhibitor enhances anthracyclines efficacy.
  
  
  CONCLUSIONS
  FOXP3 expression in tumor cells may be an accurate predictive biomarker of anthracycline efficacy in breast cancer.
authors.affiliation: Department of Medical Oncology. Centre Georges-François Leclerc, Dijon; Institut National de la Santé et de la Recherche Médicale, Avenir Team INSERM, CRI-866 University of Burgundy, Dijon.
authors.forename: S
authors.initials: S
authors.lastname: Ladoire
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Avenir Team INSERM, CRI-866 University of Burgundy, Dijon.
authors.forename: G
authors.initials: G
authors.lastname: Mignot
authors.affiliation: Biostatistics and Epidemiological Unit, EA 4184, Dijon.
authors.forename: C
authors.initials: C
authors.lastname: Dalban
authors.affiliation: Department of Medical Oncology. Centre Georges-François Leclerc, Dijon; Institut National de la Santé et de la Recherche Médicale, Avenir Team INSERM, CRI-866 University of Burgundy, Dijon.
authors.forename: A
authors.initials: A
authors.lastname: Chevriaux
authors.affiliation: Department of Pathology and Biology of Tumors.
authors.forename: L
authors.initials: L
authors.lastname: Arnould
authors.affiliation: Department of Medical Oncology. Centre Georges-François Leclerc, Dijon; Institut National de la Santé et de la Recherche Médicale, Avenir Team INSERM, CRI-866 University of Burgundy, Dijon.
authors.forename: C
authors.initials: C
authors.lastname: Rébé
authors.affiliation: Department of Medical Oncology. Centre Georges-François Leclerc, Dijon; Institut National de la Santé et de la Recherche Médicale, Avenir Team INSERM, CRI-866 University of Burgundy, Dijon.
authors.forename: L
authors.initials: L
authors.lastname: Apetoh
authors.affiliation: Molecular Genetics Laboratory, Centre Georges François Leclerc, Dijon.
authors.forename: R
authors.initials: R
authors.lastname: Boidot
authors.affiliation: Department of Pathology, Centre Jean Perrin, Clermont Ferrand.
authors.forename: F
authors.initials: F
authors.lastname: Penault-Llorca
authors.affiliation: Department of Medical Oncology. Centre Georges-François Leclerc, Dijon.
authors.forename: P
authors.initials: P
authors.lastname: Fumoleau
authors.affiliation: Department of Medical Oncology, Institut Claudius Regaud, Toulouse.
authors.forename: H
authors.initials: H
authors.lastname: Roché
authors.affiliation: Department of Medicine and Translational Research Unit, Institut Gustave Roussy, Villejuif.
authors.forename: M
authors.initials: M
authors.lastname: Spielmann
authors.affiliation: Department of Medical Oncology, Centre François Baclesse, Caen.
authors.forename: C
authors.initials: C
authors.lastname: Levy
authors.affiliation: Department of Medical Oncology, Centre Paul Papin, Angers.
authors.forename: A
authors.initials: A
authors.lastname: Lortholary
authors.affiliation: Department of Medical Oncology; Hopital Civil, Strasbourg.
authors.forename: F
authors.initials: F
authors.lastname: Eichler
authors.affiliation: Comité sein (PACS), UNICANCER, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Mesleard
authors.affiliation: Biostatistics and Epidemiological Unit, EA 4184, Dijon.
authors.forename: F
authors.initials: F
authors.lastname: Bonnetain
authors.affiliation: Department of Medical Oncology. Centre Georges-François Leclerc, Dijon; Institut National de la Santé et de la Recherche Médicale, Avenir Team INSERM, CRI-866 University of Burgundy, Dijon. Electronic address: fghiringhelli@cgfl.fr.
authors.forename: F
authors.initials: F
authors.lastname: Ghiringhelli
mesh_terms: D018943:Anthracyclines / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors