PD-L1 protein expression in breast cancer is rare, enriched in basal-like tumours and associated with infiltrating lymphocytes.
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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.
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1569-8041
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Academy of Medical Sciences (ALI 01/08/14)
Pathological Society of Great Britain & Ireland (CDF 2012/01)
Cancer Research UK (CB4140)
Cancer Research UK (unknown)
Cancer Research UK (unknown)
Cancer Research UK (60098573)
Cancer Research UK (unknown)
Department of Health (via National Institute for Health Research (NIHR)) (unknown)
Cambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
Cancer Research Uk (None)
Cambridge University Hospitals NHS Foundation Trust (CUH) (RG51913)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0515-10090)
European Commission (260791)
European Commission FP7 Network of Excellence (NoE) (260791)
Cancer Research Uk (None)
Academy of Medical Sciences (unknown)
Medical Research Council (MR/M008975/1)
European Commission FP7 Collaborative projects (CP) (258967)
Cancer Research UK (C507/A16278)
European Commission (258967)
Cancer Research UK (20544)
Medical Research Council (MR/P012442/1)
European Commission and European Federation of Pharmaceutical Industries and Associations (EFPIA) FP7 Innovative Medicines Initiative (IMI) (115749)
European Commission (242006)
European Research Council (694620)
Cancer Research UK (A24622)
Cancer Research Uk (None)
Cancer Research Uk (None)