• Matthew G Davey, Maire Caitlin Casey, Andrew McGuire, 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.
• Discipline of Surgery, Lambe Institute for Translational Research, National University of Ireland Galway, Galway, Ireland.
• Ann. Surg. 2022 Nov 1; 276 (5): 905-912.

ObjectiveTo evaluate whether circulating micro ribonucleic acids (miRNAs) predict response to neoadjuvant chemotherapy (NAC) and inform decision-making in breast cancer patients.IntroductionDeciphering response to NAC remains a challenge. Those unlikely to respond may benefit from NAC de-escalation before completion, while "responders" should complete treatment. Establishing biomarkers which identify response to NAC is imperative to personalize treatment strategies. miRNAs are small noncoding RNA molecules which modulate genetic expression. miRNAs are believed to inform response to NAC.MethodsThis prospective, multicenter trial (NCT01722851) recruited 120 patients treated with NAC across 8 Irish treatment sites. Predetermined miRNAs were quantified from patient whole bloods using relative quantification polymerase chain reactiond. Venous sampling was performed at diagnosis and midway during NAC. Trends in miRNA expression between timepoints were correlated with treatment response. Data analysis was performed using R 3.2.3.ResultsA total of 120 patients were included (median age: 55 years). Overall, 49.2% had luminal breast cancers (59/120), 17.5% luminal B (L/HER2) (21/120), 12.5% human epidermal growth factor receptor-2 positive (HER2+) (15/120), and 20.8% triple negative disease (25/120). In total, 46.7% of patients responded to NAC (56/125) and 26.7% achieved a pathological complete response (pCR) (32/120). For patients with L/HER2, increased Let-7a predicted response to NAC ( P =0.049), while decreased miR-145 predicted response to NAC in HER2+ ( P =0.033). For patients with luminal breast cancers, reduced Let-7a predicted achieving a pCR ( P =0.037) and reduced miR-145 predicted achieving a pCR to NAC in HER2+ ( P =0.027).ConclusionsThis study illustrates the potential value of circulatory miRNA measurement in predicting response to NAC. Further interrogation of these findings may see miRNAs personalize therapeutic decision-making for patients undergoing NAC for early breast cancer.Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.

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