Mohamed S. Othman,Mohamed Tharwat Elabbasy,Ahmed M. Aref,Aya A. AltalebMarwa Hamdy Mohammed,Doaa Atef Mohamed Soliman,Nashwa El-Khazragy,2024-11-062024-11-062023-10MSA Unversityhttps://repository.msa.edu.eg/handle/123456789/6189miRNA, micro-RNA; HER2-MBC, HER2-positive Metastatic Breast cancer; BC, breast cancer; BL, baseline; 1C, after completing Trastuzumab treatment; FOXP3, forkhead box P3; HER2, human epidermal growth factor receptor 2; TTP, time to progression; STROBE, Strengthening the Reporting of Observational Studies in Epidemiology; PASS, Power Analysis and Sample Size Software; ROC, Receiving operating characteristics curve; CI, 95% confidence interval; AUC, area under the curve.Purpose: Resistance to Trastuzumab is a significant challenge in the management of HER2-positive Metastatic Breast cancer (HER2-MBC), and a better understanding of the molecular causes of resistance is required to develop more effective treatment plans. While elevated plasma levels of miR-200 and FOXP3 have been linked to breast cancer progression and treatment response, no clinical studies have confirmed these results. Methods: The study involved 40 patients with HER2-positive metastatic breast cancer (HER2-MBC). The expression levels of miR-200c-3p and the FOXP3 gene were assessed in plasma samples at two time points: baseline (BL) and after the consent completion of one cycle of Trastuzumab, utilizing quantitative polymerase chain reaction (qPCR). Clinical response to Trastuzumab was evaluated 12 months post-therapy and correlated with the time to progression (TTP) through Kaplan-Meier analysis. Results: Low plasma expression level of miR-200c-3p was detected before therapy in HER2-MBC, compared to healthy controls, and decreased dramatically in the follow-up sample at disease progression, while increased after one cycle of Trastuzumab therapy in patients who were sensitive to Trastuzumab. At baseline, a low expression level of miR-200c was significantly associated with overexpression of FOXP3, poor prognosis, and shorter time to progression. Conclusions: The findings suggest that miR-200c-3p may be a promising biomarker for predicting the response to Trastuzumab in HER2-MBC patients.enTrastuzumabHER2-positive breast cancermetastatic breast cancerdrug resistancemiR-200cFOXP3predictor biomarkerArticleDOI: 10.1177/15330338241292226