Association between CD8+ T-cell infiltration and breast cancer survival in 12,439 patients

H R Ali, E Provenzano, S-J Dawson, F M Blows, B Liu, M Shah, H M Earl, C J Poole, L Hiller, J A Dunn, S J Bowden, C Twelves, J M S Bartlett, S M A Mahmoud, E Rakha, I O Ellis, S Liu, D Gao, T O Nielsen, P D P PharoahC Caldas

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: T-cell infiltration in estrogen receptor (ER)-negative breast tumours has been associated with longer survival. To investigate this association and the potential of tumour T-cell infiltration as a prognostic and predictive marker, we have conducted the largest study of T cells in breast cancer to date.

PATIENTS AND METHODS: Four studies totalling 12 439 patients were used for this work. Cytotoxic (CD8+) and regulatory (forkhead box protein 3, FOXP3+) T cells were quantified using immunohistochemistry (IHC). IHC for CD8 was conducted using available material from all four studies (8978 samples) and for FOXP3 from three studies (5239 samples)-multiple imputation was used to resolve missing data from the remaining patients. Cox regression was used to test for associations with breast cancer-specific survival.

RESULTS: In ER-negative tumours [triple-negative breast cancer and human epidermal growth factor receptor 2 (human epidermal growth factor receptor 2 (HER2) positive)], presence of CD8+ T cells within the tumour was associated with a 28% [95% confidence interval (CI) 16% to 38%] reduction in the hazard of breast cancer-specific mortality, and CD8+ T cells within the stroma with a 21% (95% CI 7% to 33%) reduction in hazard. In ER-positive HER2-positive tumours, CD8+ T cells within the tumour were associated with a 27% (95% CI 4% to 44%) reduction in hazard. In ER-negative disease, there was evidence for greater benefit from anthracyclines in the National Epirubicin Adjuvant Trial in patients with CD8+ tumours [hazard ratio (HR) = 0.54; 95% CI 0.37-0.79] versus CD8-negative tumours (HR = 0.87; 95% CI 0.55-1.38). The difference in effect between these subgroups was significant when limited to cases with complete data (P heterogeneity = 0.04) and approached significance in imputed data (P heterogeneity = 0.1).

CONCLUSIONS: The presence of CD8+ T cells in breast cancer is associated with a significant reduction in the relative risk of death from disease in both the ER-negative [supplementary Figure S1, available at Annals of Oncology online] and the ER-positive HER2-positive subtypes. Tumour lymphocytic infiltration may improve risk stratification in breast cancer patients classified into these subtypes. NEAT ClinicalTrials.gov: NCT00003577.

Original languageEnglish
Pages (from-to)1536-43
Number of pages8
JournalAnnals of Oncology
Volume25
Issue number8
DOIs
Publication statusPublished - Aug 2014

Keywords / Materials (for Non-textual outputs)

  • Adult
  • Aged
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Breast Neoplasms
  • CD8-Positive T-Lymphocytes
  • Female
  • Humans
  • Lymphocyte Count
  • Lymphocytes, Tumor-Infiltrating
  • Middle Aged
  • Predictive Value of Tests
  • Receptors, Progesterone
  • Survival Analysis
  • Triple Negative Breast Neoplasms

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