The MiR-200c/FOXP3 Network: A Promising Biomarker for Predicting Trastuzumab Response in HER2-Positive Breast Cancer

Abstract

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.

Keywords: FOXP3; HER2-positive breast cancer; Trastuzumab; drug resistance; metastatic breast cancer; miR-200c; predictor biomarker.

Figure 1.

Plasma expression levels of miR-200c-3p in HER2-MBC patients at baseline (a) and after completing the first cycle of Trastuzumab (b). Panels (c) and (d) show the plasma expression levels of FOXP3 at baseline and following the first cycle of Trastuzumab.

Figure 2.

Changes in miR-200c-3p (a) and FOXP3 (b) expression levels in HER2-MBC after completing cycle 1 of Trastuzumab. (c): Spearman's correlation analysis between miR-200c-3p and FOXP3 at BL and at 1C (d). data are presented in correlation coefficient (r) and 95% confidence intervals.

Figure 3.

The log-rank survival curve illustrates the link between the BL plasma levels of miR-200c-3p (a), FOXP3 (b), and the time to progression (TTP) in HER2-MBC, with respect to the responsiveness to trastuzumab. TTP: Time to progression.