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Association between CD8+ T-cell infiltration and breast cancer survival in 12,439 patients
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(2014) Association between CD8+ T-cell infiltration and breast cancer survival in 12,439 patients. Annals of Oncology, 25 (8). pp. 1536-1543. doi:10.1093/annonc/mdu191 ISSN 0923-7534.
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Official URL: http://dx.doi.org/10.1093/annonc/mdu191
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 (Pheterogeneity = 0.04) and approached significance in imputed data (Pheterogeneity = 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.
| Item Type: | Journal Article | ||||||
|---|---|---|---|---|---|---|---|
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Clinical Trials Unit Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Journal or Publication Title: | Annals of Oncology | ||||||
| Publisher: | Oxford University Press | ||||||
| ISSN: | 0923-7534 | ||||||
| Official Date: | 9 June 2014 | ||||||
| Dates: |
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| Volume: | 25 | ||||||
| Number: | 8 | ||||||
| Page Range: | pp. 1536-1543 | ||||||
| DOI: | 10.1093/annonc/mdu191 | ||||||
| Status: | Peer Reviewed | ||||||
| Publication Status: | Published |
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