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IRSN-23 Prospective Analyses

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE230881 | GEO | 2023/05/19

REPOSITORIES: GEO

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Project description:Trastuzumab improves survival outcomes in patients with HER2+ metastatic breast cancer. Some of these patients may become long-term survivors. The Long-Her study was designed to identify clinical and molecular markers that could differentiate long-term survivors from patients having early progression to trastuzumab. 103 patients were registered in the Long-HER study, of whom 71 had obtained a durable complete response. Median age was 58 years. Metastatic disease was diagnosed after a median of 24.7 months since primary diagnosis. Sixty-five per cent of tumours were poorly differentiated ductal carcinomas and hormonal receptors were present in 47%. Metastases were present in the liver (25%), lungs (25%), bones (23%) and soft tissues (23%), with 20% of patients having multiple locations of metastases. Median progression-free survival was 10.6 years after the diagnosis of metastatic disease. Absence of trastuzumab as part of adjuvant therapy was the only clinical factor associated with long-term survival . Gene ontology analysis demonstrated that genes involved in HIF activation, EGF receptor signalling pathway, PI3 kinase pathway, apoptosis signalling pathway and p53 pathway significantly correlated with response. The PI3K pathway was the most strongly associated with poor response to trastuzumab-based therapy: tumours in the control group usually had four or five alterations in this pathway, whereas tumours in the Long-HER group had two alterations at most. These findings support that trastuzumab may provide a substantial long-term survival benefit in a selected group of patients. Whole genome expression analysis comparing long-term survivors vs. a control group predicted early progression to trastuzumab-based therapy. Multiple alterations in genes related to the PI3K-mTOR pathway seem to be required to confer resistance to this therapy. 53 FFPE samples, which passed the RNA quality control criteria, were analyzed (45 primary tumours and 8 metastases). Among these 53 samples, 35 samples corresponded to long-term responders and 18 to the control group.

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IRSN-23 Prospective Analyses

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