Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA.
Department of Medicine, University of North Carolina, 170 Manning Drive, CB#7305 Physician's Office Building, 3119, Chapel Hill, NC, 27599-7305, USA.
Breast Cancer Res Treat. 2019 Jul;176(2):321-328. doi: 10.1007/s10549-019-05211-1. Epub 2019 Apr 23.
Brain metastases (BM) are a complication of advanced breast cancer (BC). Histology of melanoma BM offers prognostic value; however, understanding the microenvironment of breast cancer brain metastases (BCBM) is less characterized. This study reports on four histological biomarkers, gliosis, immune infiltrate, hemorrhage, necrosis, and their prognostic significance in BCBM.
A biobank of 203 human tissues from patients who underwent craniotomy for BCBM was created across four academic institutions. Degree of gliosis, immune infiltrate, hemorrhage, and necrosis were identified and scored via representative H&E stain (0-3+). Overall survival (OS) was estimated using the Kaplan-Meier method. Cox proportional hazards regression evaluated prognostic value of the biomarkers in the context of standard clinical characteristics.
BCBM subtype (available for n = 158) was 36% Her2+, 26% hormone receptor (HR)+/Her2- 38% HR-/Her2- (triple negative, TN). Gliosis was observed in 82% (116/141) of BCBM, with immune infiltrate 44% (90/201), hemorrhage 82% (166/141), and necrosis 87% (176/201). Necrosis was significantly higher in TNBC (p < 0.01). Presence of gliosis, immune infiltrate, and hemorrhage correlated with improved OS (p = 0.03, p = 0.03, p = 0.1), while necrosis correlated with inferior OS (p = 0.01). Improved OS was associated with gliosis in TN (p = 0.02), and immune infiltrate (p = 0.001) and hemorrhage (p = 0.07) in HER2+. In a multivariable model for OS, incorporating these biomarkers with traditional clinical variables improved the model fit (p < 0.001).
Gliosis confers superior prognosis in TNBC BM; immune infiltrate and hemorrhage correlate with superior prognosis in HER2+ BCBM. Understanding the metastatic microenvironment of BCBM refines prognostic considerations and may unveil novel therapeutic strategies.
脑转移（BM）是晚期乳腺癌（BC）的一种并发症。黑色素瘤 BM 的组织学具有预后价值；然而，对乳腺癌脑转移（BCBM）的微环境的了解还较少。本研究报告了四个组织学标志物，即神经胶质增生、免疫浸润、出血和坏死，以及它们在 BCBM 中的预后意义。
在四个学术机构创建了一个包含 203 个人类组织样本的生物库，这些样本来自接受颅切除术治疗 BCBM 的患者。通过代表性的 H&E 染色（0-3+）识别和评分神经胶质增生、免疫浸润、出血和坏死的程度。使用 Kaplan-Meier 方法估计总生存期（OS）。Cox 比例风险回归评估在标准临床特征背景下生物标志物的预后价值。
BCBM 亚型（可用于 n=158）为 36% Her2+、26%激素受体（HR）+/Her2-、38% HR-/Her2-（三阴性，TN）。BCBM 中有 82%（116/141）观察到神经胶质增生，44%（90/201）有免疫浸润，82%（166/141）有出血，87%（176/201）有坏死。TNBC 中坏死明显更高（p<0.01）。神经胶质增生、免疫浸润和出血的存在与 OS 改善相关（p=0.03、p=0.03、p=0.1），而坏死与 OS 降低相关（p=0.01）。在 TN 中，OS 改善与神经胶质增生相关（p=0.02），在 HER2+中与免疫浸润（p=0.001）和出血（p=0.07）相关。在 OS 的多变量模型中，将这些生物标志物与传统临床变量相结合，提高了模型拟合度（p<0.001）。
神经胶质增生在 TNBC BM 中具有较好的预后；免疫浸润和出血与 HER2+BCBM 中的较好预后相关。了解 BCBM 的转移微环境可细化预后考虑，并可能揭示新的治疗策略。
