Breast Medicine Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Medical Oncology, Duke Cancer Institute, Duke University, Durham, NC, USA.
Breast Cancer Res Treat. 2023 May;199(1):99-107. doi: 10.1007/s10549-023-06908-0. Epub 2023 Mar 17.
Tumor-infiltrating lymphocytes (TILs) have been positively correlated with response to systemic therapy for triple-negative and HER2 + subtypes and improved clinical outcomes in early breast cancer (BC). Less is known about TILs in metastatic sites, particularly brain metastases (BM), where unique immune regulation governs stromal composition. Reactive glial cells actively participate in cytokine-mediated T cell stimulation. The impact of prior medical therapy (chemotherapy, endocrine, and HER2-targeted therapy) on the presence of TILs and gliosis in human breast cancer brain metastases (BCBM) has not been previously reported.
We examined prior treatment data for 133 patients who underwent craniotomy for resection of BMs from the electronic medical record. The primary endpoint was overall survival (OS) from the time of BM diagnosis. We examined the relationship between prior systemic therapy exposure and the histologic features of gliosis, necrosis, hemorrhage, and lymphocyte infiltration (LI) in BCBMs resected at subsequent craniotomy in univariate analyses.
Complete treatment data were available for 123 patients. BCBM LI was identified in 35 of 116 (30%) patients who had received prior systemic treatment versus 5 of 7 (71.4%) who had not {significant by Fisher's exact test p = 0.045}. There were no statistically significant relationships between prior systemic therapy and the three other histologic variables examined.
This observation suggests that systemic therapy may interfere with the immune response to BCBMs and cause exhaustion of anti-tumor immunity. This motivates clinical investigation of strategies to enhance LI for therapeutic benefit to improve outcomes for patients with BCBMs.
肿瘤浸润淋巴细胞（TILs）与三阴性和 HER2 阳性亚型的全身治疗反应以及早期乳腺癌（BC）的临床结局改善呈正相关。关于转移性部位（尤其是脑转移瘤[BM]）的 TIL 知之甚少，在那里，独特的免疫调节控制着基质组成。反应性神经胶质细胞积极参与细胞因子介导的 T 细胞刺激。先前的医学治疗（化疗、内分泌和 HER2 靶向治疗）对人类乳腺癌脑转移瘤（BCBM）中 TIL 和神经胶质增生的存在的影响以前没有报道过。
我们从电子病历中检查了 133 名接受开颅手术切除 BM 的患者的先前治疗数据。主要终点是从 BM 诊断时起的总生存（OS）。我们在单变量分析中检查了先前的全身治疗暴露与 BCBM 中神经胶质增生、坏死、出血和淋巴细胞浸润（LI）的组织学特征之间的关系。
123 名患者的完整治疗数据可用。在接受过先前系统治疗的 116 名患者中有 35 名（30%）患者中发现了 BCBM LI，而在未接受过治疗的 7 名患者中有 5 名（71.4%）患者中发现了 LI{Fisher 确切检验 p=0.045，具有统计学意义}。先前的全身治疗与检查的其他三个组织学变量之间没有统计学上的显著关系。
这一观察结果表明，全身治疗可能会干扰对 BCBM 的免疫反应，并导致抗肿瘤免疫的衰竭。这促使我们对增强 LI 的策略进行临床研究，以获得治疗效益，改善 BCBM 患者的结局。
