학술논문

Evaluating the Role of Circulating MicroRNAs in Predicting Long-Term Survival Outcomes in Breast Cancer: A Prospective, Multicenter Clinical Trial.
Document Type
Article
Source
Journal of the American College of Surgeons (2563-9021). Feb2023, Vol. 236 Issue 2, p317-327. 11p.
Subject
*BREAST tumor treatment
*EVALUATION of medical care
*RESEARCH
*REVERSE transcriptase polymerase chain reaction
*CLINICAL trials
*CONFIDENCE intervals
*MICRORNA
*SURVIVAL analysis (Biometry)
*DESCRIPTIVE statistics
*DATA analysis software
*LONGITUDINAL method
Language
ISSN
2563-9021
Abstract
BACKGROUND: While long-term outcomes have improved for patients with breast cancer, 20% to 30% will still develop recurrence, and identifying these patients remains a challenge. MicroRNAs (miRNAs) are small, noncoding molecules that modulate genetic expression and affect oncogenesis. STUDY DESIGN: This prospective, multicenter trial (ICORG10/11-NCT01722851) recruited patients undergoing neoadjuvant chemotherapy across 8 Irish centers. Predetermined miRNAs were quantified from patient whole blood using quantitative reverse transcriptase polymerase chain reaction. Venous sampling was performed at diagnosis (timepoint 1) and midway during neoadjuvant chemotherapy (timepoint 2 [T2]). miRNA expression profiles were correlated with recurrence-free survival (RFS), disease-free survival (DFS), and overall survival. Data analysis was performed using R v3.2.3. RESULTS: A total of 124 patients were recruited with a median age of 55.0 years. The median follow-up was 103.1 months. Increased miR-145 expression at T2 was associated with improved RFS (hazard ratio 0.00; 95% confidence interval [CI] 0.00 to 0.99; p = 0.050). Using survival regression tree analysis, a relative cutoff of increased miR-145 expression greater than 0.222 was associated with improved RFS (p = 0.041). Increased miR-145 expression at T2 trended towards significance in predicting improved DFS (hazard ratio 0.00; 95% CI 0.00 to 1.42; p = 0.067). Using survival regression tree analysis, a relative cutoff of increased miR-145 expression greater than 0.222 was associated with improved DFS (p = 0.012). No miRNAs correlated with overall survival. CONCLUSIONs: ICORG10/11 is the first Irish multicenter, translational research trial evaluating circulatory miRNAs as biomarkers predictive of long-term survival and correlated increased miR-145 expression with enhanced outcomes in early-stage breast cancer. Validation of these findings is required in the next generation of translational research trials. This prospective, multicenter trial (ICORG10/11-NCT01722851) recruited 124 patients undergoing neoadjuvant chemotherapy (NAC). MicroRNAs were quantified from patient whole blood using real-time quantitative polymerase chain reaction during NAC. During NAC, increased miR-145 independently predicted improved recurrence- and disease-free survival. [ABSTRACT FROM AUTHOR]

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