Long-Term Prognostic Value and Analytical Parameters of the Next-Generation Sequencing-Based Multigene Assay in Hormone Receptor-Positive, HER2-Negative Breast Cancer

Hyunji Kim ¹, Jiwon Koh ², Hyunwoo Lee ³

¹Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
²Department of Pathology, Seoul National University Hospital, Seoul, Korea.
³Department of Pathology and Translational Genomics, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, Korea.
⁴Department of Pathology, University of Ulsan, College of Medicine, Asan Medical Centre, Seoul, Korea.
⁵Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.
⁶Medical Research Collaborating Centre, Seoul National University Hospital, Seoul, Korea.
⁷Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
⁸Division of Breast Surgery, Department of Surgery, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, Korea.
⁹Division of Breast Surgery, Department of Surgery, Asan Medical Centre, University of Ulsan College of Medicine, Seoul, Korea.
¹⁰Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.
¹¹Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.
¹²Cancer Research Institute, Seoul National University, Seoul, Korea.

⁰Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

Cancer Research and Treatment +

|

September 4, 2025

View abstract on PubMed

Summary

This study validates a next-generation sequencing (NGS) assay for predicting distant recurrence in hormone receptor-positive, HER2-negative early breast cancer. Stringent quality control is crucial for accurate prognostic assessment.

Area Of Science

Oncology
Genomics
Clinical Diagnostics

Background

Gene expression testing guides treatment for HR-positive, HER2-negative early breast cancer.
A novel next-generation sequencing (NGS) assay was developed to improve accessibility and representation in clinical trials.
This study focuses on validating the long-term prognostic capability and quality control (QC) of this NGS assay.

Purpose Of The Study

To validate the long-term prognostic value of an NGS-based assay in HR-positive, HER2-negative early breast cancer.
To analyze the performance of quality control (QC) parameters for the NGS assay.
To assess the assay's utility across diverse patient demographics, including younger and premenopausal individuals.

Main Methods

Analysis of 265 breast cancer patient samples with over 10 years of follow-up.
Evaluation of the NGS assay's prognostic stratification using the Decision Index (DI) for distant recurrence risk.
Assessment of key QC parameters, including DV200 and cDNA concentrations, and their impact on prognostic accuracy.

Main Results

The NGS assay effectively stratified patients into low- and high-risk groups for distant recurrence, with significant differences in 10-year metastasis-free survival.
In younger patients (≤50 years), the high-risk group identified by the assay showed a substantially increased hazard ratio for recurrence (5.89).
Samples failing stringent QC criteria demonstrated diminished prognostic value, highlighting the importance of parameters like DV200 and cDNA concentration.

Conclusions

The NGS-based assay is validated for its ability to predict long-term distant recurrence risk in HR-positive/HER2-negative early breast cancer.
Stringent quality control is essential to ensure the reliability and prognostic accuracy of the NGS assay.
The validated assay supports improved treatment decisions and clinical trial representation for diverse patient populations.

Keywords:

Breast neoplasms Hormone receptor Multigene assay Next-generation sequencing Prognostic value Quality control RNA expression analysis