title: Patients with metastatic breast cancer leading to CD4+ T cell lymphopaenia have poor outcome.
abstract: BACKGROUND
  Low lymphocyte count is a prognostic factor in cancer patients including metastatic breast cancer patients (MBC) but the relative role of each lymphocyte subtype is unclear in MBC.
  
  
  METHODS
  The impact of lymphocyte subsets was analysed in two prospective MBC patients' cohorts. Cohort A patients (n=103) were included before the first line of chemotherapy and cohort B patients (n=101) were included after at least one line of chemotherapy. Extensive phenotypic analyses were performed on fresh whole blood. Plasma cytokines levels were measured using commercially available Luminex-based multiplex kits. Prognostic value of lymphocyte subsets and circulating cytokines was analysed.
  
  
  RESULTS
  In both cohorts, severe lymphopaenia (<0.7 Giga/L) correlated with poor overall survival (OS) (median OS: 6.6 months versus 21.7 months in cohort A and 4.5 versus 9 months in cohort B). CD8(+), CD19(+) and CD56(+) T cell counts had no significant prognostic value for OS. After stratification (≤0.2, [0.20-0.45], >0.45 Giga/L), CD4 lymphopaenia appeared to be correlated with poor OS in both cohorts. Furthermore, severe CD4(+) lymphopaenia (≤0.2 Giga/L) was strongly correlated with poor OS in both cohorts (1.2 months versus 24.9 months in cohort A and 5.7 versus 13.1 months in cohort B). In multivariate analysis, after stratification CD4(+) lymphopaenia appeared to be an independent prognostic factor for OS in both cohorts. CD4(+) lymphopaenia correlated with low plasmatic levels of CCL22 that might directly contribute to CD4(+) lymphopaenia.
  
  
  CONCLUSIONS
  CD4(+) lymphopaenia was associated with reduced OS in MBC patients regardless of the chemotherapy line. Decreased levels of plasmatic CCL22 may contribute to CD4(+) lymphopaenia.
authors.affiliation: Department of Medical Oncology, Centre Léon Bérard, 28 rue Laennec, Lyon 69008, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Trédan
authors.forename: Manuarii
authors.initials: M
authors.lastname: Manuel
authors.forename: Gilles
authors.initials: G
authors.lastname: Clapisson
authors.forename: Thomas
authors.initials: T
authors.lastname: Bachelot
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chabaud
authors.forename: Christine
authors.initials: C
authors.lastname: Bardin-dit-Courageot
authors.forename: Chantal
authors.initials: C
authors.lastname: Rigal
authors.forename: Cathy
authors.initials: C
authors.lastname: Biota
authors.forename: Agathe
authors.initials: A
authors.lastname: Bajard
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pasqual
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Blay
authors.forename: Christophe
authors.initials: C
authors.lastname: Caux
authors.forename: Christine
authors.initials: C
authors.lastname: Ménétrier-Caux
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D054422:Chemokine CCL22 / Q000097:blood / Q000276:immunology; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008231:Lymphopenia / Q000097:blood / Q000276:immunology*; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D011379:Prognosis; D013997:Time Factors
chemical_list: D054422:Chemokine CCL22; D016207:Cytokines