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

Purpose: In hormone receptor (HR)-positive, HER2-negative early breast cancer, gene expression testing facilitates treatment decisions. A next-generation sequencing (NGS)-based assay was developed to address test decentralization and underrepresentation of younger/premenopausal patients. We aimed to validate the long-term prognostic value of the NGS-based assay and analyze its quality control (QC) parameters.

Materials and methods: We analyzed samples from 265 patients with breast cancer with at least 10 years of follow-up. We evaluated the long-term prognostic ability of the NGS-based assay according to the risk groups for distant recurrence, as determined by the Decision Index (DI), and the performance of the QC parameters used for the experimental process.

Results: Among 265 participants, 60.4% were ≤50 years old, and 39 (14.7%) experienced distant recurrence within 10 years. In the DI-stratified low- and high-risk groups (n=186; 70.2% and n=79; 29.8%), 10-year distant metastasis-free survival rates were 96.1% (95% CI 92.1-98.1) and 79.3% (95% CI 68.4-86.8), respectively. In patients aged ≤50 years, the high-risk group had a hazard ratio of 5.89 (95% CI 2.84-12.20). Analyses including 106 samples that failed the stringent QC criteria showed inferior prognostic value, wherein DV200 and cDNA concentrations were the most crucial parameters.

Conclusion: We validated the prognostic ability of an NGS-based assay to stratify HR-positive/HER2-negative breast cancers and predict the risk of distant recurrence, and confirmed the requirement for stringent QC criteria to ensure its prognostic ability.