Clinicopathological and prognostic significance of programmed cell death ligand 1 expression in patients diagnosed with breast cancer: meta-analysis

Background: Uncertainty exists regarding the clinical relevance of programmed cell death ligand 1 (PD-L1) expression in breast cancer. Methods: A systematic review was performed in accordance with PRISMA guidelines. Observational studies that compared high versus low expression of PD-L1 on breast cancer cells were identified. Log hazard ratios (HRs) for disease-free and overall survival and their standard errors were calculated from Kaplan-Meier curves or Cox regression analyses, and pooled using the inverse-variance method. Dichotomous variables were pooled as odds ratios (ORs) using the Mantel-Haenszel method. Results: Sixty-five studies with 19 870 patients were included; 14 404 patients were classified as having low and 4975 high PD-L1 expression. High PD-L1 was associated with achieving a pathological complete response following neoadjuvant chemotherapy (OR 3.30, 95 per cent confidence interval 1.19 to 9.16; P< 0.01; I-2 = 85 per cent). Low PD-L1 expression was associated with human epidermal growth factor receptor 2 (OR 3.98, 1.81 to 8.75; P< 0.001; I-2 = 96 per cent) and luminal (OR 14.93, 6.46 to 34.51; P< 0.001; I-2 = 99 per cent) breast cancer subtypes. Those with low PD-L1 had favourable overall survival rates (HR 1.30, 1.05 to 1.61; P = 0.02; I-2 = 85 per cent). Conclusion: Breast cancers with high PD-L1 expression are associated with aggressive clinicopathological and immunohistochemical characteristics and are more likely to achieve a pathological complete response following neoadjuvant chemotherapy. These breast cancers are, however, associated with worse overall survival outcomes.