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Background: Expression of programmed death ligand 1 (PD-L1) in solid tumours has been shown to predict whether patients are likely to respond to anti-PD-L1 therapies. To estimate the therapeutic potential of PD-L1 inhibition in breast cancer, we evaluated the prevalence and significance of PD-L1 protein expression in a large collection of breast tumours., Patients and Methods: Correlations between CD274 (PD-L1) copy number, transcript and protein levels were evaluated in tumours from 418 patients recruited to the METABRIC genomic study. Immunohistochemistry was used to detect PD-L1 protein in breast tumours in tissue microarrays from 5763 patients recruited to the SEARCH population-based study (N = 4079) and the NEAT randomised, controlled trial (N = 1684)., Results: PD-L1 protein data was available for 3916 of the possible 5763 tumours from the SEARCH and NEAT studies. PD-L1 expression by immune cells was observed in 6% (235/3916) of tumours and expression by tumour cells was observed in just 1.7% (66/3916). PD-L1 was most frequently expressed in basal-like tumours. This was observed both where tumours were subtyped by combined copy number and expression profiling [39% (17/44) of IntClust 10 i.e. basal-like tumours were PD-L1 immune cell positive; P < 0.001] and where a surrogate IHC-based classifier was used [19% (56/302) of basal-like tumours were PD-L1 immune cell positive; P < 0.001]. Moreover, CD274 (PD-L1) amplification was observed in five tumours of which four were IntClust 10. Expression of PD-L1 by either tumour cells or infiltrating immune cells was positively correlated with infiltration by both cytotoxic and regulatory T cells (P < 0.001). There was a nominally significant association between PD-L1 and improved disease-specific survival (hazard ratio 0.53, 95% confidence interval 0.26-1.07; P = 0.08) in ER-negative disease., Conclusions: Expression of PD-L1 is rare in breast cancer, markedly enriched in basal-like tumours and is correlated with infiltrating lymphocytes. PD-L1 inhibition may benefit the 19% of patients with basal-like tumours in which the protein is expressed., Neat Clinicaltrialsgov: NCT00003577., (© The Author 2015. 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.)

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., (© 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.)