• Matthew G Davey, Andrew McGuire, Maire Caitlin Casey, Ronan M Waldron, Maxwell Paganga, Emma Holian, John Newell, Helen M Heneghan, Ailbhe M McDermott, Maccon M Keane, Aoife J Lowery, Nicola Miller, and Michael J Kerin.
• From the Discipline of Surgery, Lambe Institute for Translational Research, National University of Ireland Galway, Galway, Ireland (Davey, McGuire, Casey, Waldron, Heneghan, McDermott, Lowery, Miller, Kerin).
• J. Am. Coll. Surg. 2023 Feb 1; 236 (2): 317327317-327.

BackgroundWhile 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 DesignThis 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.ResultsA 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.ConclusionsICORG10/11 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.Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Surgeons.

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