title: T-bet expression in intratumoral lymphoid structures after neoadjuvant trastuzumab plus docetaxel for HER2-overexpressing breast carcinoma predicts survival.
abstract: BACKGROUND
  In HER2-overexpressing breast cancer, accumulating preclinical evidences suggest that some chemotherapies, like trastuzumab, but also taxanes, are able to trigger a T helper 1 (Th1) anticancer immune response that contribute to treatment success. T helper 1 immune response is characterised by the expression of the transcription factor T-bet in CD4 T lymphocytes. We hypothesised that the presence of such T cells in the tumour immune infiltrates following neoadjuvant chemotherapy would predict patient survival.
  
  
  METHODS
  In a series of 102 consecutive HER2-overexpressing breast cancer patients treated by neoadjuvant chemotherapy incorporating antracyclines or taxane and trastuzumab, we studied by immunohistochemistry the peritumoral lymphoid infiltration by T-bet+ lymphocytes before and after chemotherapy in both treatment groups. Kaplan-Meier analysis and Cox modelling were used to assess relapse-free survival (RFS).
  
  
  RESULTS
  Fifty-eight patients have been treated with trastuzumab-taxane and 44 patients with anthracyclines-based neoadjuvant chemotherapy. The presence of T-bet+ lymphocytes in peritumoral lymphoid structures after chemotherapy was significantly more frequent in patients treated with trastuzumab-taxane (P=0.0008). After a median follow-up of 40 months, the presence of T-bet+ lymphocytes after neoadjuvant chemotherapy confers significantly better RFS (log-rank test P=0.011) only in patients treated with trastuzumab-taxane. In this population, multivariate Cox regression model showed that only the presence of T-bet+ lymphocytes in peritumoral lymphoid structures after neoadjuvant chemotherapy was independently associated with improved RFS (P=0.04).
  
  
  CONCLUSIONS
  These findings indicate that the tumour infiltration by T-bet+ Th1 lymphocytes following neoadjuvant trastuzumab-taxane may represent a new independent prognostic factor of improved outcome in HER2-overexpressing breast carcinoma.
authors.affiliation: Department of Medical Oncology, Georges François Leclerc Center, Centre de Recherche INSERM 866, Faculté de Médecine, 7 Boulevard Jeanne d'Arc, Dijon 21000, France.
authors.forename: S
authors.initials: S
authors.lastname: Ladoire
authors.forename: L
authors.initials: L
authors.lastname: Arnould
authors.forename: G
authors.initials: G
authors.lastname: Mignot
authors.forename: L
authors.initials: L
authors.lastname: Apetoh
authors.forename: C
authors.initials: C
authors.lastname: Rébé
authors.forename: F
authors.initials: F
authors.lastname: Martin
authors.forename: P
authors.initials: P
authors.lastname: Fumoleau
authors.forename: B
authors.initials: B
authors.lastname: Coudert
authors.forename: F
authors.initials: F
authors.lastname: Ghiringhelli
mesh_terms: D018943:Anthracyclines; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000401:mortality; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D000077143:Docetaxel; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D008221:Lymphoid Tissue / Q000378:metabolism*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011379:Prognosis; D020825:T-Box Domain Proteins / Q000378:metabolism*; D043823:Taxoids / Q000008:administration & dosage*; D000068878:Trastuzumab; D000098815:T-bet Transcription Factor
chemical_list: D018943:Anthracyclines; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D043823:Taxoids; D000077143:Docetaxel; D000068878:Trastuzumab