Caroline Boman1, Ioannis Zerdes2, Kira Mårtensson3, Jonas Bergh2, Theodoros Foukakis2, Antonios Valachis4, Alexios Matikas2. 1. Department of Oncology-Pathology, Karolinska Institutet Visionsgatan 4, Bioclinicum, 171 74 Stockholm, Sweden; Breast Center, Theme Cancer, Karolinska University Hospital, Stockholm, Gävlegatan 55, 171 64 Solna, Sweden. Electronic address: caroline.boman@ki.se. 2. Department of Oncology-Pathology, Karolinska Institutet Visionsgatan 4, Bioclinicum, 171 74 Stockholm, Sweden; Breast Center, Theme Cancer, Karolinska University Hospital, Stockholm, Gävlegatan 55, 171 64 Solna, Sweden. 3. Department of Clinical Pathology and Cytology, Karolinska University Laboratory, 171 76 Stockholm, Sweden. 4. Department of Oncology, Faculty of Medicine and Health, Örebro University, 701 82 Örebro, Sweden.
Abstract
INTRODUCTION: 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.
INTRODUCTION:Programmed cell death ligand 1 (PD-L1) expression is predictive for benefit from immunotherapy in several humanmalignancies 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.
Authors: Carlos Alexander Huertas-Caro; Mayra Alejandra Ramirez; Henry J Gonzalez-Torres; María Carolina Sanabria-Salas; Silvia J Serrano-Gómez Journal: Front Oncol Date: 2022-07-18 Impact factor: 5.738