Validation of the predictive ability for recurrence and the clinical utility of the 95-gene classifier (95GC) through an integrated analysis of five studies.

Background In recent years, multigene assays have become indispensable tools for predicting the recurrence risk of estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer and guiding adjuvant chemotherapy decisions. Curebest™ 95GC Breast (95GC), developed in 2011 as a domestically produced multigene assay for postoperative recurrence prediction, has been commercially available since 2013. Since 2021, five validation studies evaluating the predictive performance 95GC have been published. This study presents an integrated analysis of these studies to validate the prognostic utility of 95GC further. Methods The integrated analysis included 719 real-world cases of luminal-type node-negative breast cancer patients who underwent adjuvant hormone therapy alone without extended endocrine treatment. Additionally, an expanded cohort incorporating 294 cases from Western patients within the GEO public database was analyzed, resulting in a total of 1,013 cases. Results Among the 719 real-world cases, 550 (76.5%) were classified into the 95GC Low-risk group, demonstrating a significantly superior prognosis compared to the High-risk group (P < 1.00e-12). The 5-year distant recurrence-free survival (DRFS) rate in the Low-risk group was approximately 98%, with consistent findings observed in the expanded cohort. Furthermore, an analysis of 754 CEL files using 21GC (a proxy for Oncotype DX®) identified 318 cases (42.2%) as the 21GC intermediate risk. 95GC successfully stratified these cases into two prognostically distinct subgroups. Conclusions These findings underscore the clinical utility of 95GC in safely omitting chemotherapy for Low-risk patients with good prognosis and in further stratifying the 21GC Intermediate-risk cases, thereby contributing to personalized treatment strategies.