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

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

来源：Annals of Oncology, 2014, 25(8): 1536-1543.

DOI：10.1093/annonc/mdu191

• breast cancer
• lymphocytes
• inflammation
• chemotherapy
• molecular subtypes

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.

• 出版日期2014-8