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Background <p>This study evaluates the reproducibility of the IRSN-23 model, which classifies patients into highly chemotherapy-sensitive (Gp-R) or less-sensitive (Gp-NR) groups based on immune-related gene expression using DNA microarray analysis, and its impact on breast cancer subtype classification.</p> Methods <p>Tumor tissues from 146 breast cancer patients receiving neoadjuvant chemotherapy (paclitaxel-FEC) ± trastuzumab at Osaka University Hospital (OUH) were used to classify patients into Gp-R or Gp-NR using IRSN-23. The ability to predict a pathological complete response (pCR) was assessed and the results were validated with independent public datasets (N = 1282).</p> Results <p>In the OUH dataset, the pCR rate was significantly higher in the Gp-R group than in the Gp-NR group without trastuzumab (29 versus 1%, P = 1.70E−5). In all validation sets without anti-HER2 therapy, the pCR rate in the Gp-R group was significantly higher than that in the Gp-NR group. The pooled analysis of the validation set showed higher pCR rates in the Gp-R group than in the Gp-NR group, both without (N = 1103, 40 versus 12%, P = 2.02E−26) and with (N = 304, 49 versus 35%, P = 0.017) anti-HER2 therapy. Collaboration analyses of IRSN-23 and Oncotype Dx or PAM50 could identify highly chemotherapy-sensitive groups and refine breast cancer subtype classification based on the tumor microenvironment (offensive factor—PAM50 and defensive factor—IRSN-23), and the immune subtype was correlated with a better prognosis after NAC.</p> Conclusions <p>This study offers new validation analyses of IRSN-23 in predicting chemotherapy efficacy, showing high reproducibility. The findings indicate the clinical value of using IRSN-23 for refining breast cancer subtype classification, with implications for personalized treatment strategies and improved patient outcomes.</p>

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IRSN-23 gene diagnosis enhances breast cancer subtype classification and predicts response to neoadjuvant chemotherapy: new validation analyses

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月24日

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  • Yoshiaki Sota,
  • Shigeto Seno,
  • Yasuto Naoi,
  • Keiichiro Honma,
  • Masafumi Shimoda,
  • Tomonori Tanei,
  • Hideo Matsuda,
  • Kenzo Shimazu

摘要

Background

This study evaluates the reproducibility of the IRSN-23 model, which classifies patients into highly chemotherapy-sensitive (Gp-R) or less-sensitive (Gp-NR) groups based on immune-related gene expression using DNA microarray analysis, and its impact on breast cancer subtype classification.

Methods

Tumor tissues from 146 breast cancer patients receiving neoadjuvant chemotherapy (paclitaxel-FEC) ± trastuzumab at Osaka University Hospital (OUH) were used to classify patients into Gp-R or Gp-NR using IRSN-23. The ability to predict a pathological complete response (pCR) was assessed and the results were validated with independent public datasets (N = 1282).

Results

In the OUH dataset, the pCR rate was significantly higher in the Gp-R group than in the Gp-NR group without trastuzumab (29 versus 1%, P = 1.70E−5). In all validation sets without anti-HER2 therapy, the pCR rate in the Gp-R group was significantly higher than that in the Gp-NR group. The pooled analysis of the validation set showed higher pCR rates in the Gp-R group than in the Gp-NR group, both without (N = 1103, 40 versus 12%, P = 2.02E−26) and with (N = 304, 49 versus 35%, P = 0.017) anti-HER2 therapy. Collaboration analyses of IRSN-23 and Oncotype Dx or PAM50 could identify highly chemotherapy-sensitive groups and refine breast cancer subtype classification based on the tumor microenvironment (offensive factor—PAM50 and defensive factor—IRSN-23), and the immune subtype was correlated with a better prognosis after NAC.

Conclusions

This study offers new validation analyses of IRSN-23 in predicting chemotherapy efficacy, showing high reproducibility. The findings indicate the clinical value of using IRSN-23 for refining breast cancer subtype classification, with implications for personalized treatment strategies and improved patient outcomes.