Investigating the Association of the Biogenic Amine Profile in Urine with Therapeutic Response to Neoadjuvant Chemotherapy in Breast Cancer Patients.

Neoadjuvant treatment (NAT) can downstage breast cancer and can be utilized for different clinical applications. However, the response to NAT varies among individuals. Having effective biomarkers is important to optimize the treatment of breast cancer. Concentrations of biogenic amines have been found to show an association with cancer cell proliferation, but their clinical utility remains unclear. This study developed a postcolumn-infused internal standard (PCI-IS)-assisted liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) method for profiling biogenic amines in human urine. Putrescine-d8 was selected as the PCI-IS to calibrate the errors caused by matrix effects in the urine sample. The optimized method was applied to investigate the association between changes in 14 amines and the therapeutic response to NAT in breast cancer patients. Urine samples were collected before initiation of chemotherapy (n = 60). Our results indicated that the levels of N1-acetylspermine, spermidine, norepinephrine, and dopamine were significantly higher in the responder group than the nonresponder group. These metabolites were incorporated with clinical factors to identify NAT responders, and the prediction model showed an area under the curve value of 0.949. These observations provide remarkable insights for future studies in elucidating the roles of biogenic amines in breast cancer. Additionally, the PCI-IS-assisted amine profiling method can facilitate these studies.