Inhibition of the PD-1/PD-ligand1 (PD-L1) axis has shown considerable therapeutic promise in several cancers. Tumor PD-L1 protein expression may predict response to drugs targeting this pathway, but its measurement has been limited by the lack of standardized immunohistochemical methods and variable antibody performance.
In a study reported in Clinical Cancer Research, Schalper and colleagues observed consistent measurements of in situ PD-L1 mRNA levels in 636 stage I to III breast carcinomas using two different sets of tissue microarrays and found that increased PD-L1 mRNA expression was associated with increased numbers of tumor-infiltrating lymphocytes and prolonged recurrence-free survival. The two microarrays showed PD-L1 mRNA expression in 55.7% and 59.5% of cases, with higher PD-L1 mRNA expression being significantly associated with increased tumor-infiltrating lymphocytes (P = .04) but not with other clinical variables.
Elevated tumor-infiltrating lymphocytes were found in 16.5% and 14.8% of samples with the two microarrays and were associated with estrogen receptor–negative status (P = .01 and P = .0001). PD-L1 mRNA expression was significantly associated with longer recurrence-free survival (P = .01), with the significant association persisting on multivariate analysis including age, tumor size, histologic grade, nodal metastasis, hormone receptor status, HER2 status, and extent of tumor-infiltrating lymphocytes (hazard ratio = 0.268, P = .009).
The investigators concluded, “PD-L1 mRNA expression is identified in nearly 60% of breast tumors and it is associated with increased [tumor-infiltrating lymphocytes] and improved recurrence-free survival. These observations support the evaluation of PD-1/PD-L1-targeted therapies in breast cancer.” ■
Schalper KA, et al: Clin Cancer Res 20:1-10, 2014.