Baek Seung Ho, Kim Jee Hung, Bae Soong June, Ji Jung Hwan, Lee Yangkyu, Jeong Joon, Cha Yoon Jin, Ahn Sung Gwe
Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea.
Institute of Breast Cancer Precision Medicine, Yonsei University College of Medicine, Seoul 06273, Korea.
Cancers (Basel). 2022 Jun 21;14(13):3042. doi: 10.3390/cancers14133042.
The discernible PD-L1 staining of tumor-infiltrating lymphocytes occupying ≥ 1% of the tumor area is considered SP142 PD-L1 positive for atezolizumab, and the PD-L1 status of multiple samples within a single patient could be discrepant. In this study, we evaluated the PD-L1 status by using the SP142 clone in serially collected matched samples from the same individuals with early or metastatic triple-negative breast cancer (TNBC).
the SP142 PD-L1 assay was performed using biopsies and surgical specimens from 77 patients with early TNBC. Among these patients, 47 underwent upfront surgery, and 30 underwent neoadjuvant chemotherapy (NAC) between biopsy and surgery. PD-L1 assays were performed at least twice in 8/12 (66.7%) patients with metastatic TNBC treated with atezolizumab and nab-paclitaxel.
Of the 47 patients who underwent upfront surgery, 15/47 (31.9%) had PD-L1+ on biopsied samples. PD-L1+ rates in the biopsy and surgical specimens increased to 66.0% (33 of 47) after subsequent surgery. Similarly, in the 30 patients with residual invasive cancer who underwent neoadjuvant chemotherapy, the PD-L1+ rate increased from 46.6% at baseline to 74.2% after surgery. In the 77 patients with early TNBC, multiple PD-L1 testing in the biopsies and surgical specimens significantly increased the number of patients with PD-L1+ compared with the number of patients with PD-L1+ assessed with initial biopsy samples alone (68.8% vs. 37.6%; = 0.00002). Among the metastatic TNBC patients, those with constant PD-L1+ over 1% positivity in multiple samples showed a response which was longer than 12 months.
Our findings reveal the heterogeneous SP142 PD-L1 expression in TNBC and suggest that PD-L1 evaluation in baseline biopsy might be insufficient to represent the PD-L1 status of whole tumors. In TNBC, vigorous PD-L1 examination using multiple available tumor samples could identify more patients eligible for immune checkpoint blockade.
肿瘤浸润淋巴细胞的可辨别的程序性死亡配体1（PD-L1）染色占据肿瘤面积的≥1%被认为对于阿特珠单抗而言SP142 PD-L1呈阳性，并且同一患者体内多个样本的PD-L1状态可能存在差异。在本研究中，我们使用SP142克隆评估了来自早期或转移性三阴性乳腺癌（TNBC）个体的系列收集的匹配样本中的PD-L1状态。
使用77例早期TNBC患者的活检组织和手术标本进行SP142 PD-L1检测。在这些患者中，47例接受了 upfront手术，30例在活检和手术之间接受了新辅助化疗（NAC）。对8/12（66.7%）例接受阿特珠单抗和纳米白蛋白紫杉醇治疗的转移性TNBC患者进行了至少两次PD-L1检测。
在47例接受 upfront手术的患者中，15/47（31.9%）例活检样本的PD-L1呈阳性。后续手术后，活检和手术标本中的PD-L1阳性率增至66.0%（47例中的33例）。同样，在30例接受新辅助化疗的残留浸润性癌患者中，PD-L1阳性率从基线时的46.6%增至术后的74.2%。在77例早期TNBC患者中，与仅用初始活检样本评估的PD-L1阳性患者数量相比，活检和手术标本中的多次PD-L1检测显著增加了PD-L1阳性患者数量（68.8%对37.6%；P = 0.00002）。在转移性TNBC患者中，多个样本中PD-L1持续阳性超过1%的患者显示出超过12个月的反应。
我们的研究结果揭示了TNBC中SP142 PD-L1表达的异质性，并表明基线活检中的PD-L1评估可能不足以代表整个肿瘤的PD-L1状态。在TNBC中，使用多个可用肿瘤样本进行积极的PD-L1检测可以识别出更多符合免疫检查点阻断治疗条件的患者。
