Patients with metastatic breast cancer leading to CD4+ T cell lymphopaenia have poor outcome

Eur J Cancer. 2013 May;49(7):1673-82. doi: 10.1016/j.ejca.2012.11.028. Epub 2012 Dec 19.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Breast Neoplasms / blood
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / pathology
  • Chemokine CCL22 / blood
  • Chemokine CCL22 / immunology
  • Cohort Studies
  • Cytokines / blood
  • Cytokines / immunology*
  • Female
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Lymphopenia / blood
  • Lymphopenia / immunology*
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Metastasis
  • Prognosis
  • Time Factors

Substances

  • Chemokine CCL22
  • Cytokines