title: CD4+CD25+ regulatory T-cell frequency in HER-2/neu (HER)-positive and HER-negative advanced-stage breast cancer patients.
abstract: OBJECTIVE
  CD4(+)CD25(bright) regulatory T cells (Tregs) are increased in patients with several malignancies and correlate with disease stage and prognosis. Breast cancer patients represent a heterogeneous population with unpredictable disease progression even at advanced stages. Circulating Tregs in correlation with HER-2/neu (HER) status and treatment with chemotherapy, either alone or in combination with trastuzumab therapy, were monitored in advanced-stage breast cancer patients.
  
  
  METHODS
  Circulating Treg frequency and absolute counts of 46 HER(+) and 28 HER(-), stage III and IV, breast cancer patients before therapy and during trastuzumab therapy and/or chemotherapy have been compared with 24 healthy donors and correlated with plasma HER extracellular domain concentration and clinical outcome.
  
  
  RESULTS
  Treg frequency in HER(+) patients was significantly increased compared with both HER(-) patients and healthy donors. Trastuzumab therapy, with or without combined chemotherapy, resulted in a progressive decrease of circulating Tregs. Percentage change in Tregs statistically correlated with percentage change in plasma HER extracellular domain. Furthermore, decrease in Tregs correlated with either objective clinical response or stable disease, whereas increased Treg frequency during trastuzumab therapy coincided with disease progression. No statistically significant change in Treg frequency following chemotherapy was observed in HER(-) patients.
  
  
  CONCLUSIONS
  Treg cell frequency does not directly correlate with clinical stage in breast cancer, as stage III and IV HER(+) and HER(-) patients exhibit significantly different Treg profiles. Trastuzumab therapy, either alone or combined with chemotherapy, results in decreased Treg frequency in HER(+) advanced patients with an objective clinical response.
authors.affiliation: Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, Athens, Greece. perez@ciic.gr
authors.forename: Sonia A
authors.initials: SA
authors.lastname: Perez
authors.forename: Michael V
authors.initials: MV
authors.lastname: Karamouzis
authors.forename: Dimosthenes V
authors.initials: DV
authors.lastname: Skarlos
authors.forename: Alexandros
authors.initials: A
authors.lastname: Ardavanis
authors.forename: Nectaria N
authors.initials: NN
authors.lastname: Sotiriadou
authors.forename: Eleni G
authors.initials: EG
authors.lastname: Iliopoulou
authors.forename: Maria L
authors.initials: ML
authors.lastname: Salagianni
authors.forename: George
authors.initials: G
authors.lastname: Orphanos
authors.forename: Constantin N
authors.initials: CN
authors.lastname: Baxevanis
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Rigatos
authors.forename: Michael
authors.initials: M
authors.lastname: Papamichail
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D015704:CD4 Antigens / Q000032:analysis; D005260:Female; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D018655:Lymphocyte Count; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab