Purpose: Conflicting data have been reported on the prognostic value of PD-L1 protein and gene expression in breast cancer. Experimental Design: Medline, Embase, Cochrane Library, and Web of Science Core Collection were searched, and data were extracted independently by two researchers. Outcomes included pooled PD-L1 protein positivity in tumor cells, immune cells, or both, per subtype and per antibody used, and its prognostic value for disease-free and overall survival. A pooled gene expression analysis of 39 publicly available transcriptomic datasets was also performed. Results: Of the initial 4,184 entries, 38 retrospective studies fulfilled the predefined inclusion criteria. The overall pooled PD-L1 protein positivity rate was 24% (95% CI, 15%-33%) in tumor cells and 33% (95% CI, 14%-56%) in immune cells. PD-L1 protein expression in tumor cells was prognostic for shorter overall survival (HR, 1.63; 95% CI, 1.07-2.46; P ¼ 0.02); there was significant heterogeneity (I 2 ¼ 80%, P heterogeneity < 0.001). In addition, higher PD-L1 gene expression predicted better survival in multivariate analysis in the entire population (HR, 0.82; 95% CI, 0.74-0.90; P < 0.001 for OS) and in basal-like tumors (HR, 0.64; 95% CI, 0.52-0.80; P < 0.001 for OS; P interaction 0.005). Conclusions: The largest to our knowledge meta-analysis on the subject informs on PD-L1 protein positivity rates and its prognostic value in breast cancer. Standardization is needed prior to routine implementation. PD-L1 gene expression is a promising prognostic factor, especially in basal-like breast cancer. Discrepant prognostic information might be related to PD-L1 gene expression in the stroma.
This study found obesity to be an independent risk factor for local complications, of erysipelas. Hence, obese patients with erysipelas are prone to complications, and should be carefully evaluated because of the potential severity of disease and the increased risk of failure of empirical antimicrobial therapy.
Programmed cell death ligand 1 (PD-L1) expression is predictive for benefit from immunotherapy in several human malignancies including triple negative breast cancer. Lower positivity rates but a larger relative benefit from atezolizumab has been implied when PD-L1 status is assessed at metastatic sites. We aimed to study the discordance of PD-L1 expression between primary tumor and metastasis in breast cancer due to its potential clinical utility. Methods: Cochrane Library, Embase, Medline and Web of science were searched for studies reporting on PD-L1 expression in primary and metastatic breast cancer, followed by data extraction. Outcomes included pooled PD-L1 positivity rates in tumor cells, immune cells or both in primary tumor and metastasis, PD-L1 discordance between matched primary tumors and metastasis and direction of discordance. Results: Of 2552 identified entries following de-duplication, 20 studies fulfilled the predefined inclusion criteria. Pooled PD-L1 positivity rate was higher in primary tumors compared to metastasis when assessed in immune cells (51.2% vs 37.1% p < 0.001) and tumor/immune cells (30.1% vs 14.6% p < 0.001), but not in tumor cells (18.7% vs 17.8% p = 0.65). PD-L1 positivity was lowest when assessed in bone metastases (12%) and highest in lymph nodes (60%). Discordance between primary tumors and metastasis was bidirectional, with higher pooled discordance rates when PD-L1 expression was assessed in immune compared to tumor cells (39.5% vs 13.6%, p < 0.001).
Conclusion:The observed considerable discordance between PD-L1 status in primary and metastatic breast cancer emphasizes the importance of appropriate tissue sampling when selecting patients for immunotherapy.
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