In situ immune response after neoadjuvant chemotherapy for breast cancer predicts survival

J Pathol. 2011 Jul;224(3):389-400. doi: 10.1002/path.2866. Epub 2011 Mar 25.


Accumulating preclinical evidence suggests that anticancer immune responses contribute to the success of chemotherapy. However, the predictive value of tumour-infiltrating lymphocytes after neoadjuvant chemotherapy for breast cancer remains unknown. We hypothesized that the nature of the immune infiltrate following neoadjuvant chemotherapy would predict patient survival. In a series of 111 consecutive HER2- and a series of 51 non-HER2-overexpressing breast cancer patients treated by neoadjuvant chemotherapy, we studied by immunohistochemistry tumour infiltration by FOXP3 and CD8 T lymphocytes before and after chemotherapy. Kaplan-Meier analysis and Cox modelling were used to assess relapse-free survival (RFS) and overall survival (OS). A predictive scoring system using American Joint Committee on Cancer (AJCC) pathological staging and immunological markers was created. Association of high CD8 and low FOXP3 cell infiltrates after chemotherapy was significantly associated with improved RFS (p = 0.02) and OS (p = 0.002), and outperformed classical predictive factors in multivariate analysis. A combined score associating CD8/FOXP3 ratio and pathological AJCC staging isolated a subgroup of patients with a long-term overall survival of 100%. Importantly, this score also identified patients with a favourable prognosis in an independent cohort of HER2-negative breast cancer patients. These results suggest that immunological CD8 and FOXP3 cell infiltrate after treatment is an independent predictive factor of survival in breast cancer patients treated with neoadjuvant chemotherapy and provides new insights into the role of the immune milieu and cancer.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Chemotherapy, Adjuvant
  • Epidemiologic Methods
  • Female
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Lymphocytes, Tumor-Infiltrating / drug effects*
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Staging
  • Prognosis
  • Receptor, ErbB-2 / metabolism
  • Treatment Outcome


  • Biomarkers, Tumor
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • ERBB2 protein, human
  • Receptor, ErbB-2