期刊
ANNALS OF ONCOLOGY
卷 25, 期 8, 页码 1536-1543出版社
OXFORD UNIV PRESS
DOI: 10.1093/annonc/mdu191
关键词
breast cancer; lymphocytes; inflammation; chemotherapy; molecular subtypes
类别
资金
- Cancer Research UK [C490/A10119, C490/A10124]
- NIHR Cambridge Biomedical Research Centre
- Addenbrooke's Charitable Trust
- Career Development Fellowship from the Pathological Society of Great Britain and Northern Ireland
- Sanofi-Aventis Canada
- Government of Egypt
- Breast Cancer Campaign
- MRC [G0300648] Funding Source: UKRI
- Academy of Medical Sciences (AMS) [AMS-SGCL11-Ali] Funding Source: researchfish
- Cancer Research UK [16561, 16942] Funding Source: researchfish
- Medical Research Council [G0300648] Funding Source: researchfish
- National Institute for Health Research [CL-2013-14-006, NF-SI-0611-10154] Funding Source: researchfish
- The Francis Crick Institute
- Cancer Research UK [10124] Funding Source: researchfish
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据