Department of Microbiology, and Immunology and Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, 621 Rubin Building-HB7936, 1 Medical Center Drive, Lebanon, NH, 03756, USA.
Departments of Pathology and Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Breast Cancer Res Treat. 2021 Dec;190(3):477-489. doi: 10.1007/s10549-021-06391-5. Epub 2021 Sep 20.
This study evaluated epidemiologic and immune factors associated with pathologic complete response (pCR), breast cancer-specific survival (BCSS) and disease-free survival (DFS) outcomes in inflammatory (IBC) and locally advanced breast cancer (LABC) patients.
Tumor-infiltrating lymphocytes (TILs) and CD20 B-cell frequencies (CD20), and PD-L1 expression on tumor (PD-L1carcinoma cells) and immune (PD-L1TILs) cells were analyzed by immunohistochemistry along with clinicopathologic factors as modifiers of pCR and outcomes in 221 IBC and 162 LABC patients. Analysis included Kaplan-Meier curves and Cox proportional hazard models.
IBC and LABC display similar levels of TILs, CD20, and combined CD20 and PD-L1TILs (CD20PD-L1TILs), while LABC contained more PD-L1TILs and PD-L1 carcinoma cells. Absence of lymphovascular involvement, high TILs, PD-L1 carcinoma cells, and combined CD20 and PD-L1 carcinoma cells correlated with pCR in IBC and LABC patients. High PD-L1TILs correlated with pCR only in LABC; less lymph node involvement at diagnosis, CD20 and CD20PD-L1TILs correlated with pCR only in IBC (P < 0.04, all comparisons). Achievement of pCR in IBC and LABC patients correlated with BCSS and DFS (P < 0.02). In multivariate analyses, pCR remained an independent prognostic factor of improved DFS in IBC and LABC patients, but of BCSS in only LABC. CD20PD-L1TILs remained an independent prognostic factor of improved DFS and BCSS only in IBC.
CD20PD-L1TILs are an independent prognostic biomarker of improved outcomes in IBC, but not LABC. Selecting IBC patients by CD20 and PD-L1 status could stratify patients and potentially identify those in whom activating CD20 agents and anti-PD-1/PD-L1 therapy could be explored.
本研究评估了与炎性乳腺癌（IBC）和局部晚期乳腺癌（LABC）患者的病理完全缓解（pCR）、乳腺癌特异性生存（BCSS）和无病生存（DFS）结局相关的流行病学和免疫因素。
通过免疫组织化学分析肿瘤浸润淋巴细胞（TILs）和 CD20 B 细胞频率（CD20）以及肿瘤（PD-L1 癌细胞）和免疫（PD-L1TILs）上的 PD-L1 表达，并结合临床病理因素，作为 pCR 和 221 例 IBC 和 162 例 LABC 患者结局的调节剂。分析包括 Kaplan-Meier 曲线和 Cox 比例风险模型。
IBC 和 LABC 显示出相似水平的 TILs、CD20 和 CD20 和 PD-L1TILs 联合（CD20PD-L1TILs），而 LABC 含有更多的 PD-L1TILs 和 PD-L1 癌细胞。无淋巴血管浸润、高 TILs、PD-L1 癌细胞和 CD20 和 PD-L1 癌细胞联合与 IBC 和 LABC 患者的 pCR 相关。高 PD-L1TILs 仅与 LABC 中的 pCR 相关；诊断时较少的淋巴结受累、CD20 和 CD20PD-L1TILs 仅与 IBC 中的 pCR 相关（所有比较 P<0.04）。IBC 和 LABC 患者获得 pCR 与 BCSS 和 DFS 相关（P<0.02）。在多变量分析中，pCR 仍然是 IBC 和 LABC 患者改善 DFS 的独立预后因素，但仅在 LABC 中是 BCSS 的独立预后因素。CD20PD-L1TILs 仍然是 IBC 中改善 DFS 和 BCSS 的独立预后因素。
CD20PD-L1TILs 是 IBC 患者改善结局的独立预后生物标志物，但不是 LABC。通过 CD20 和 PD-L1 状态选择 IBC 患者可以对患者进行分层，并可能确定那些可以探索激活 CD20 药物和抗 PD-1/PD-L1 治疗的患者。
