The Prognostic Value of PD-L1 Expression in Triple-Negative Breast Cancer: A Cohort Study and Systematic Literature Review

Abstract

Context The prognostic value of programmed death ligand-1 (PD-L1) in triple-negative breast cancer (TNBC) is unclear. Objective To investigate PD-L1 expression for association with survival. Design Surgical specimens of primary TNBC were linked to data on recurrence-free survival (RFS). Tissue microarray averaging 3 tumor cores per case underwent immunohistochemical staining. Within each core, PD-L1 positivity was scored separately for tumor, stromal, and immune cells by averaging readings by two board-certified pathologists. Having at least one core with high (above 10%) PD-L1 staining (on tumor cells as primary risk, on stromal and immune cells as secondary risks) was evaluated for association with RFS using proportional hazards regression. Comparable survival analyses were identified by systematic search of MEDLINEindexed journals through March 2019. Results Patients (n=112) contributed 308 cores of TNBC. During follow-up, TNBC recurred in 24 subjects; another 4 subjects died without recurrence. Ten (8.9%) subjects had High PD-L1 expression on tumor cells, a feature associated with better RFS [hazards ratio 0.44 (95% Confidence Interval 0.19-0.97)] independently of age, distant metastasis, tumor size, lymphovascular invasion, and Ki-67. In contrast, High PD-L1 in stromal cells or immune cells was not associated with RFS. Among 22 similar studies, high PDL1 on tumor cells was associated with survival in 16 studies: 7 favorably, 8 unfavorably, and 1 with mixed results. Conclusions In this TNBC cohort, High PD-L1 on tumor cells conferred favorable prognosis. The lack of consensus across similar studies suggests that future studies should explore how timing, microenvironment, and glycosylation influence PD-L1’s association with survival.