Plasma metabolomic signatures associated with pathologic complete response in locally advanced breast cancer following neoadjuvant chemotherapy

Reliable biomarkers associated with pathological complete response (pCR) following neoadjuvant chemotherapy (NAC) remain limited. We therefore conducted an exploratory longitudinal metabolomic study to identify candidate plasma metabolites associated with treatment response in patients with breast cancer undergoing NAC. Thirty patients were prospectively enrolled between July and November 2021. Of these, 20 with complete longitudinal plasma samples were included in the final analysis. Plasma samples were collected longitudinally from diagnosis through surgery. Targeted metabolomic profiling was performed using the AbsoluteIDQ ® p400 HR kit. Of the 408 measured metabolites, 213 were consistently detected across all samples and included in the analysis. Among the 20 patients analyzed, 8 achieved pCR and 12 did not. Seven candidate metabolites showed nominally significant differences between the pCR and non-pCR groups at diagnosis. Because HER2 receptor expression differed significantly between the groups ( p = 0.04), longitudinal analyses were performed using HER2-adjusted linear mixed-effects models. Distinct metabolite trajectories were observed between response groups, and PC(42:0) and PC(32:5) remained significantly associated with treatment response after Benjamini–Hochberg false discovery rate (FDR) correction. This exploratory longitudinal metabolomic study identified PC(42:0) and PC(32:5) as candidate metabolites showing distinct longitudinal patterns according to NAC treatment response. No metabolites remained significant at diagnosis after FDR correction. These findings should be considered hypothesis-generating and warrant validation in larger prospective cohorts.