PD-L1 protein expression in breast cancer is rare, enriched in basal-like tumours and associated with infiltrating lymphocytes
Menée à partir d'échantillons tumoraux prélevés sur 418 et 5 763 patientes atteintes d'un cancer du sein, cette étude montre que l'expression de la protéine PD-L1 est rare mais plus fréquente dans les tumeurs de type "basal-like", puis met en évidence une association entre l'expression de PD-L1 et l'infiltration des lymphocytes dans la tumeur
Background : Expression of 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% CI 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.
Annals of Oncology , résumé, 2015