Association between CD8+ T-cell infiltration and breast cancer survival in 12,439 patients - PubMed (original) (raw)
Clinical Trial
. 2014 Aug;25(8):1536-43.
doi: 10.1093/annonc/mdu191. Epub 2014 Jun 9.
E Provenzano 2, S-J Dawson 3, F M Blows 4, B Liu 3, M Shah 5, H M Earl 6, C J Poole 7, L Hiller 7, J A Dunn 7, S J Bowden 8, C Twelves 9, J M S Bartlett 10, S M A Mahmoud 11, E Rakha 11, I O Ellis 11, S Liu 12, D Gao 12, T O Nielsen 12, P D P Pharoah 5, C Caldas 13
Affiliations
- PMID: 24915873
- DOI: 10.1093/annonc/mdu191
Free article
Clinical Trial
Association between CD8+ T-cell infiltration and breast cancer survival in 12,439 patients
H R Ali et al. Ann Oncol. 2014 Aug.
Free article
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.
Keywords: breast cancer; chemotherapy; inflammation; lymphocytes; molecular subtypes.
© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Comment in
- The immunogenicity of breast cancer--molecular subtypes matter.
Denkert C. Denkert C. Ann Oncol. 2014 Aug;25(8):1453-5. doi: 10.1093/annonc/mdu235. Epub 2014 Jun 20. Ann Oncol. 2014. PMID: 24950977 No abstract available.
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