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.
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.
Cancer Treat Rev. 2021 Sep;99:102257. doi: 10.1016/j.ctrv.2021.102257. Epub 2021 Jul 1.
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.
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.
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).
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.
程序性死亡配体 1（PD-L1）的表达在包括三阴性乳腺癌在内的几种人类恶性肿瘤中对免疫治疗有预测作用。在转移性部位评估 PD-L1 状态时，较低的阳性率但更大的相对获益暗示着阿替利珠单抗的疗效。我们旨在研究乳腺癌中原发肿瘤和转移灶之间 PD-L1 表达的不一致性，因为它具有潜在的临床应用价值。
检索 Cochrane 图书馆、Embase、Medline 和 Web of Science 中关于原发性和转移性乳腺癌中 PD-L1 表达的研究，并进行数据提取。主要结局为肿瘤细胞、免疫细胞或两者的 PD-L1 阳性率，原发肿瘤和转移灶的 PD-L1 不一致性以及不一致的方向。
在去重后 2552 个条目中，有 20 项研究符合预先设定的纳入标准。当评估免疫细胞时，与转移灶相比，原发肿瘤中的 PD-L1 阳性率更高（51.2%比 37.1%，p<0.001）和肿瘤/免疫细胞（30.1%比 14.6%，p<0.001），但在肿瘤细胞中则不然（18.7%比 17.8%，p=0.65）。在骨转移中 PD-L1 阳性率最低（12%），在淋巴结中最高（60%）。原发肿瘤和转移灶之间的不一致是双向的，当评估免疫细胞中的 PD-L1 表达时，其汇总不一致率更高（39.5%比 13.6%，p<0.001）。
观察到原发性和转移性乳腺癌中 PD-L1 状态存在相当大的不一致性，这强调了在选择免疫治疗患者时适当组织取样的重要性。
