A Randomized Trial of miRNA-34a-Based Therapy for Chemosensitization in Triple-Negative Breast Cancer Patients

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Rida Zainab
Azhar Rashid
Attiq Ullah
Taqdees Mehmood
Hadiya Rafique
Mahgul Noor
Ayesha Saeed

Abstract

Background: Triple-negative breast cancer is an aggressive malignancy with limited targeted treatment options and variable response to neoadjuvant chemotherapy. Restoring tumor-suppressive miRNA-34a activity may improve chemosensitivity. Objective: To determine whether adding a liposomal miRNA-34a mimic to standard neoadjuvant chemotherapy increases pathological complete response in stage II–III triple-negative breast cancer. Methods: This prospective, two-arm randomized controlled trial was conducted at a tertiary cancer Centre in urban Sindh, Pakistan, from May 2025 to January 2026. Eighty-four women were randomized equally to dose-dense AC-T chemotherapy with weekly intravenous liposomal miRNA-34a mimic or chemotherapy alone. Pathologists were blinded to allocation. Outcomes were analyzed for 80 participants with postoperative data using chi-square tests, t-tests, repeated-measures analysis of variance, and Pearson correlation. Results: Pathological complete response occurred in 62.5% of intervention participants and 35.0% of controls (risk difference, 27.5%; 95% CI, 6.4–48.6; p=0.014). Residual tumor diameter was lower with combination therapy (1.1±0.8 vs 2.2±1.1 cm; mean difference, −1.10 cm; 95% CI, −1.53 to −0.67; p<0.001). The time-by-group interaction for tumor regression was significant (F(2,156)=14.86; p<0.001). Conclusion: Liposomal miRNA-34a combined with neoadjuvant chemotherapy demonstrated a preliminary improvement in pathological and imaging responses, although confirmation requires complete randomized and safety analyses

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[1]
Rida Zainab et al. 2026. A Randomized Trial of miRNA-34a-Based Therapy for Chemosensitization in Triple-Negative Breast Cancer Patients. Journal of Health, Wellness and Community Research. 4, 5 (Mar. 2026), 1–7. DOI:https://doi.org/10.61919/hxwqyv32.

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