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脑转移是晚期乳腺癌的并发症之一。虽然已知黑色素瘤脑转移的微环境组织学特征具有预后意义，但是乳腺癌脑转移的微环境组织学特征尚不明确。 2019年4月23日，施普林格·自然《乳腺癌研究与治疗》在线发表美国莱恩伯格综合癌症中心、北卡罗来纳大学教堂山分校、亚特兰大抗癌协会、南卡罗来纳医科大学、礼来、杜克大学、哈佛大学医学院达纳法伯癌症研究所、匹兹堡大学、密歇根大学、纽约纪念医院斯隆凯特林癌症中心的研究报告，分析了乳腺癌脑转移的微环境组织学生物标志、胶质增生、免疫浸润、出血、坏死及其预后意义。 该研究通过四个学术机构建立的203例乳腺癌脑转移开颅手术患者人体组织生物库，确定胶质增生、免疫浸润、出血、坏死的程度，根据苏木精伊红染色进行评分（0～+++）。通过生存曲线法，推算总生存。通过多因素比例风险回归模型分析，评估标准临床特征生物标志对总生存的预测意义。 结果，对158例乳腺癌脑转移进行亚型分析，其中HER2阳性占36%、激素受体阳性占26%、三阴性占38%。 乳腺癌脑转移可见胶质增生116/141例（82%）、免疫浸润90/201例（44%）、出血166/141例（82%）、坏死176/201例（87%）。坏死显著多见于三阴性乳腺癌（P < 0.01）。 单因素分析表明，胶质增生、免疫浸润、出血分别与总生存改善显著相关（P = 0.03、P = 0.03、P = 0.1），坏死与总生存恶化显著相关（P = 0.01）。 双因素分析表明，三阴性乳腺癌胶质增生、HER2阳性乳腺癌免疫浸润和出血与总生存改善显著相关（P = 0.02、P = 0.001、P = 0.07）。 多因素分析表明，这些生物标志结合传统临床因素，可以显著提高对总生存的预测意义（P < 0.001）。 因此，该研究结果表明，胶质增生对于三阴性乳腺癌脑转移的预后意义较大，免疫浸润和出血对于HER2阳性乳腺癌脑转移的预后意义较大。明确乳腺癌脑转移的微环境组织学特征，可以细化预后因素，并且可能发现新的治疗策略。 Breast Cancer Res Treat. 2019 Apr 23. Examination and prognostic implications of the unique microenvironment of breast cancer brain metastases. Maria J. Sambade, Grace Prince, Allison M. Deal, Dimitri Trembath, Megan McKee, Amy Garrett, Kevin Keith, Juanita Ramirez, Bentley Midkiff, Kimberly Blackwell, Sarah Sammons, Jose Pablo Leone, Adam Brufsky, Aki Morikawa, Edi Brogi, Andrew Seidman, Matthew Ewend, Lisa A. Carey, Stergios J. Moschos, Ronald L. Hamilton, Benjamin Vincent, Carey Anders. Lineberger Comprehensive Cancer Center, Chapel Hill, USA; University of North Carolina, Chapel Hill, USA; Atlanta Cancer Care, Atlanta, Georgia; Medical University of South Carolina, Charleston, USA; Eli Lilly, Indianapolis, USA; Duke University, Durham, USA; Dana Farber Cancer Institute, Boston, USA; University of Pittsburgh, Pittsburgh, USA; University of Michigan, Ann Arbor, USA; Memorial Sloan Kettering Cancer Center, New York, USA. PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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. KEYWORDS: Breast cancer brain metastases; Immune infiltrate; Microenvironment; Prognosis DOI: 10.1007/s10549-019-05211-1
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