IRSN-23 Prospective Analyses. IRSN-23 Prospective Analyses

PURPOSE: The IRSN-23 model uses DNA microarray analysis of tumor tissue to personalize patients into highly sensitive chemotherapy (Gp-R) or less sensitive (Gp-NR) based on the expression of immune-related genes. This study assessed the reproducibility of the IRSN-23 in prospective independent validation sets and investigated its clinical significance and impact on breast cancer subtype classification. METHODS: Tumour tissues were collected from 146 breast cancer patients undergoing preoperative chemotherapy (paclitaxel-FEC) ± trastuzumab in Osaka University Hospital (OUH). Patients were classified into Gp-R or Gp-NR using IRSN-23, and the model was examined for its ability to predict the pathological complete response (pCR). RESULTS: In the OUH prospective dataset, the pCR rate was significantly higher in the Gp-R group (29·3% (11/41)) than in the Gp-NR group (1·4% (1/71)) not using trastuzumab (P = 1·70E-5). CONCLUSION: This study provides prospective validation of the IRSN-23 in predicting chemotherapy efficacy, demonstrating a high degree of reproducibility. Overall design: Fresh frozen tumor samples obtained by vacuum-assisted core biopsy from two hundred and sixty three patients were subjected to RNA extraction and hybridization on Affymetrix microarrays.

研究目的：IRSN-23模型通过对肿瘤组织开展DNA微阵列分析（DNA microarray analysis），依据免疫相关基因的表达水平，将患者划分为高敏感化疗组（Gp-R）与低敏感化疗组（Gp-NR）。本研究旨在评估IRSN-23在前瞻性独立验证队列中的可重复性，并探究其临床意义以及对乳腺癌亚型分类的影响。
研究方法：本研究从大阪大学医院（OUH）纳入146例接受术前化疗（紫杉醇-FEC方案）联合或不联合曲妥珠单抗的乳腺癌患者，采集其肿瘤组织。采用IRSN-23模型将患者划分为Gp-R组与Gp-NR组，并评估该模型预测病理完全缓解（pathological complete response, pCR）的能力。
研究结果：在大阪大学医院的前瞻性数据集当中，未使用曲妥珠单抗的患者亚组中，Gp-R组的病理完全缓解率为29.3%（11/41），显著高于Gp-NR组的1.4%（1/71）（P=1.70×10^-5）。
研究结论：本研究在前瞻性队列中验证了IRSN-23模型预测化疗疗效的效能，证实其具备良好的可重复性。
整体研究设计：本研究对263例患者通过真空辅助空心针活检获取的新鲜冰冻肿瘤样本开展RNA提取，并在Affymetrix微阵列上进行杂交反应。