An evaluation of the clinical significance of FOXP3+ infiltrating cells in human breast cancer

Breast Cancer Res Treat. 2011 May;127(1):99-108. doi: 10.1007/s10549-010-0987-8. Epub 2010 Jun 17.

Abstract

Studies in mice have shown that thymic-derived CD4+ CD25+ regulatory T cells (T reg; FOXP3(+) lymphocytes) inhibit an antitumour immune response. Additional studies have also reported that the T reg population increases in peripheral blood and tumour tissues from patients with cancer. However, the relationship between the T reg population and the patient prognosis remains controversial. Our aim was to determine the prognostic value of T reg cell density in breast cancer using immunohistochemical assessment of FOXP3, which has been shown to be the optimal marker for T regs. Tissue microarrays were used, and the density of FOXP3(+) cells was determined in a series of 1445 cases of well-characterised primary invasive breast carcinoma cases with long-term follow up. FOXP3(+) cell numbers were counted in tumour nests, in tumour-adjacent stroma, and in distant stroma. The total number of FOXP3(+) cells significantly correlated with higher tumour grade (r (s) = 0.37, P < 0.001) and ER negativity (Mann-Whitney U test, P < 0.001). In addition, FOXP3 infiltration positively correlated with HER2 expression and basal phenotype subclass. On univariate analysis, FOXP3(+) cells were associated with a worse prognosis (P = 0.012, log rank = 6.36). This association was found for intratumoural FOXP3(+) and for tumour-adjacent stromal FOXP3(+)-cells (tumour-cell associated FOXP3, P = 0.001 and log rank 10.35). However, the number of FOXP3(+) cells was not found to be an independent prognostic factor in multivariate analysis. We therefore conclude that FOXP3(+) infiltrating cells do not have a dominant role in breast cancer prognosis and suggest that other inflammatory cell subsets may be more critical variables.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Chemotherapy, Adjuvant
  • Female
  • Forkhead Transcription Factors / metabolism*
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Receptors, Estrogen / metabolism
  • Retrospective Studies
  • Survival Analysis
  • Treatment Outcome

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Receptors, Estrogen