Immune checkpoint inhibitor therapies targeting PD-1/PD-L1 are now the standard of care in oncology across several hematologic and solid tumor types, including triple negative breast cancer (TNBC). Patients with metastatic or locally advanced TNBC with PD-L1 expression on immune cells occupying ≥1% of tumor area demonstrated survival benefit with the addition of atezolizumab to nab-paclitaxel. However, concerns regarding variability between immunohistochemical PD-L1 assay performance and inter-reader reproducibility have been raised. High tumor-infiltrating lymphocytes (TILs) have also been associated with response to PD-1/PD-L1 inhibitors in patients with breast cancer (BC). TILs can be easily assessed on hematoxylin and eosin-stained slides and have shown reliable inter-reader reproducibility. As an established prognostic factor in early stage TNBC, TILs are soon anticipated to be reported in daily practice in many pathology laboratories worldwide. Because TILs and PD-L1 are parts of an immunological spectrum in BC, we propose the systematic implementation of combined PD-L1 and TIL analyses as a more comprehensive immuno-oncological biomarker for patient selection for PD-1/PD-L1 inhibition-based therapy in patients with BC. Although practical and regulatory considerations differ by jurisdiction, the pathology community has the responsibility to patients to implement assays that lead to optimal patient selection. We propose herewith a risk-management framework that may help mitigate the risks of suboptimal patient selection for immuno-therapeutic approaches in clinical trials and daily practice based on combined TILs/PD-L1 assessment in BC. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

中文翻译：

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通往更好生物标志物的道路：应用风险管理框架在乳腺癌临床试验和日常实践中实施 PD-L1 和 TIL 作为免疫肿瘤生物标志物。

针对 PD-1/PD-L1 的免疫检查点抑制剂疗法现在已成为包括三阴性乳腺癌 (TNBC) 在内的多种血液和实体肿瘤类型的肿瘤治疗标准。转移性或局部晚期 TNBC 患者在免疫细胞上 PD-L1 表达占 ≥ 1% 的肿瘤区域证明了在白蛋白结合型紫杉醇中添加阿特珠单抗后的生存获益。然而，人们对免疫组化 PD-L1 检测性能和阅读器间重现性之间的差异性提出了担忧。高肿瘤浸润淋巴细胞 (TIL) 也与乳腺癌 (BC) 患者对 PD-1/PD-L1 抑制剂的反应有关。TIL 可以在苏木精和伊红染色的载玻片上轻松评估，并显示出可靠的阅读器间重现性。作为早期 TNBC 的既定预后因素，预计 TIL 很快将在全球许多病理学实验室的日常实践中报告。由于 TIL 和 PD-L1 是 BC 免疫谱的一部分，我们建议系统实施 PD-L1 和 TIL 联合分析，作为基于 PD-1/PD-L1 抑制的患者选择的更全面的免疫肿瘤生物标志物BC 患者的治疗。尽管实际和监管方面的考虑因司法管辖区而异，但病理学界有责任让患者实施能够实现最佳患者选择的检测。我们在此提出了一个风险管理框架，该框架可能有助于降低基于 BC 联合 TIL/PD-L1 评估的临床试验和日常实践中免疫治疗方法选择不理想的患者风险。© 2020 大不列颠及爱尔兰病理学会。约翰威利父子公司出版