Metabolomic changes associated with treatment response of neoadjuvant chemotherapy with TEC regimen in HER2-negative breast cancer

Abstract

Introduction: This study aimed to characterize time-dependent metabolic alterations and identify metabolites associated with treatment response in HER2-negative breast cancer patients undergoing neoadjuvant chemotherapy (NAC) with the TEC regimen (docetaxel, epirubicin, and cyclophosphamide). Methods: A total of 60 plasma samples were collected from 20 patients at three time points: baseline (T1), after three cycles of NAC (T2), and before surgery (T3). Pathological assessment classified patients into three response groups: pathologic complete response (pCR, n = 5), pathologic partial response (pPR, n = 7), and pathologic stable disease (pSD, n = 8). Results: After three cycles of NAC, a greater decrease in glycochenodeoxycholate was associated with poorer treatment response, whereas a larger reduction in LysoPC(18:1) correlated with better response. Following six cycles, elevated epinephrine levels were positively associated with therapeutic efficacy, while increased cysteine levels were linked to unfavorable outcomes. Ursodeoxycholic acid showed an upward trend in pCR patients but declined in pPR and pSD groups. Combined analysis of ursodeoxycholic acid and cysteine improved the predictive performance for treatment response. Discussion: These findings reveal dynamic metabolic reprogramming during NAC and suggest that ursodeoxycholic acid and cysteine may serve as potential predictive biomarkers of therapeutic efficacy in HER2-negative breast cancer patients treated with the TEC regimen.