激素受体/HER2 阳性早期乳腺癌的肿瘤免疫微环境与新辅助化疗反应
Tumor Immune Microenvironment and Response to Neoadjuvant Chemotherapy in Hormone Receptor/HER2+ Early Stage Breast Cancer.
机构信息
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
Division of Medical Oncology, Columbia University Irving Medical Center, New York, NY.
出版信息
Clin Breast Cancer. 2022 Aug;22(6):538-546. doi: 10.1016/j.clbc.2022.04.002. Epub 2022 Apr 18.
BACKGROUND
Pathologic response at the time of surgery after neoadjuvant therapy for HER2 positive early breast cancer impacts both prognosis and subsequent adjuvant therapy. Comprehensive descriptions of the tumor microenvironment (TME) in patients with HER2 positive early breast cancer is not well described. We utilized standard stromal pathologist-assessed tumor infiltrating lymphocyte (TIL) quantification, quantitative multiplex immunofluorescence, and RNA-based gene pathway signatures to assess pretreatment TME characteristics associated pathologic complete response in patients with hormone receptor positive, HER2 positive early breast cancer treated in the neoadjuvant setting.
METHODS
We utilized standard stromal pathologist-assessed TIL quantification, quantitative multiplex immunofluorescence, and RNA-based gene pathway signatures to assess pretreatment TME characteristics associated pathologic complete response in 28 patients with hormone receptor positive, HER2 positive early breast cancer treated in the neoadjuvant setting.
RESULTS
Pathologist-assessed stromal TILs were significantly associated with pathologic complete response (pCR). By quantitative multiplex immunofluorescence, univariate analysis revealed significant increases in CD3+, CD3+CD8-FOXP3-, CD8+ and FOXP3+ T-cell densities as well as increased immune cell aggregates in pCR patients. In subsets of paired pre/post-treatment samples, we observed significant changes in gene expression signatures in non-pCR patients and significant decreases in CD8+ densities after treatment in pCR patients. No RNA based pathway signature was associated with pCR.
CONCLUSION
TME characterization HER2 positive breast cancer patients revealed several stromal T-cell densities and immune cell aggregates associated with pCR. These results demonstrate the feasibility of these novel methods in TME evaluation and contribute to ongoing investigations of the TME in HER2+ early breast cancer to identify robust biomarkers to best identify patients eligible for systemic de-escalation strategies.
背景
曲妥珠单抗为基础的新辅助治疗后 HER2 阳性早期乳腺癌患者的手术病理反应不仅影响预后，还影响后续辅助治疗。目前尚缺乏对 HER2 阳性早期乳腺癌患者肿瘤微环境（TME）的全面描述。本研究利用标准的间质病理评估肿瘤浸润淋巴细胞（TIL）定量、定量多重免疫荧光和基于 RNA 的基因通路特征，评估了激素受体阳性、HER2 阳性早期乳腺癌患者新辅助治疗中与病理完全缓解（pCR）相关的 TME 特征。
方法
我们利用标准的间质病理评估肿瘤浸润淋巴细胞（TIL）定量、定量多重免疫荧光和基于 RNA 的基因通路特征，评估了激素受体阳性、HER2 阳性早期乳腺癌患者新辅助治疗中与病理完全缓解（pCR）相关的 TME 特征。
结果
病理评估的间质 TIL 与 pCR 显著相关。通过定量多重免疫荧光，单因素分析显示 pCR 患者的 CD3+、CD3+CD8-FOXP3-、CD8+和 FOXP3+T 细胞密度以及免疫细胞聚集体显著增加。在配对的治疗前/后样本亚组中，我们观察到非 pCR 患者的基因表达特征发生了显著变化，pCR 患者的 CD8+密度在治疗后显著下降。没有 RNA 通路特征与 pCR 相关。
结论
对 HER2 阳性乳腺癌患者的 TME 特征进行分析，揭示了几种与 pCR 相关的基质 T 细胞密度和免疫细胞聚集体。这些结果证明了这些新方法在 TME 评估中的可行性，并为进一步研究 HER2+早期乳腺癌的 TME 以确定强有力的生物标志物，从而更好地识别适合系统降阶策略的患者提供了依据。
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