title: PD-L1 protein expression in breast cancer is rare, enriched in basal-like tumours and associated with infiltrating lymphocytes.
abstract: 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.
  
  
  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.
  NCT00003577.
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge Department of Pathology, University of Cambridge, Cambridge raza.ali@cruk.cam.ac.uk.
authors.forename: H R
authors.initials: HR
authors.lastname: Ali
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge.
authors.forename: S-E
authors.initials: SE
authors.lastname: Glont
authors.affiliation: Department of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge.
authors.forename: F M
authors.initials: FM
authors.lastname: Blows
authors.affiliation: Department of Histopathology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge Cambridge Experimental Cancer Medicine Centre and NIHR Cambridge Biomedical Research Centre, Cambridge.
authors.forename: E
authors.initials: E
authors.lastname: Provenzano
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge Department of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge Cambridge Experimental Cancer Medicine Centre and NIHR Cambridge Biomedical Research Centre, Cambridge.
authors.forename: S-J
authors.initials: SJ
authors.lastname: Dawson
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge.
authors.forename: B
authors.initials: B
authors.lastname: Liu
authors.affiliation: Warwick Clinical Trials Unit, University of Warwick, Coventry.
authors.forename: L
authors.initials: L
authors.lastname: Hiller
authors.affiliation: Warwick Clinical Trials Unit, University of Warwick, Coventry.
authors.forename: J
authors.initials: J
authors.lastname: Dunn
authors.affiliation: Warwick Clinical Trials Unit, University of Warwick, Coventry.
authors.forename: C J
authors.initials: CJ
authors.lastname: Poole
authors.affiliation: Cancer Research UK Clinical Trials Unit, Institute for Cancer Studies, The University of Birmingham, Edgbaston, Birmingham.
authors.forename: S
authors.initials: S
authors.lastname: Bowden
authors.affiliation: Department of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge Cambridge Experimental Cancer Medicine Centre and NIHR Cambridge Biomedical Research Centre, Cambridge.
authors.forename: H M
authors.initials: HM
authors.lastname: Earl
authors.affiliation: Department of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge Strangeways Research Laboratory, University of Cambridge, Cambridge, UK.
authors.forename: P D P
authors.initials: PD
authors.lastname: Pharoah
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge Department of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge Cambridge Experimental Cancer Medicine Centre and NIHR Cambridge Biomedical Research Centre, Cambridge.
authors.forename: C
authors.initials: C
authors.lastname: Caldas
mesh_terms: D060890:B7-H1 Antigen / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002280:Basal Cell Carcinoma / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging; D064887:Observational Studies as Topic; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D046888:Tissue Array Analysis
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor
keywords: CD274; PD-L1; basal-like; breast cancer; immune checkpoint; lymphocytes