T-bet Expression in Intratumoral Lymphoid Structures After Neoadjuvant Trastuzumab Plus Docetaxel for HER2-overexpressing Breast Carcinoma Predicts Survival

Br J Cancer. 2011 Jul 26;105(3):366-71. doi: 10.1038/bjc.2011.261. Epub 2011 Jul 12.

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).

Conclusion: 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.

MeSH terms

  • Anthracyclines
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / immunology
  • Breast Neoplasms / mortality
  • CD4-Positive T-Lymphocytes / metabolism*
  • Docetaxel
  • Female
  • Genes, erbB-2*
  • Humans
  • Lymphoid Tissue / metabolism*
  • Middle Aged
  • Neoadjuvant Therapy
  • Prognosis
  • T-Box Domain Proteins / metabolism*
  • Taxoids / administration & dosage*
  • Trastuzumab

Substances

  • Anthracyclines
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Taxoids
  • Docetaxel
  • Trastuzumab