e15041 Background: The spatial and temporal heterogeneity of tumors in breast cancer pose challenges in precision oncology. Although breast imaging during screening has increased tumor detection and reduced mortality rates, it is limited in tracking minimal residual disease after surgery. Consequently, there is a need for liquid biopsy with easy longitudinal sampling to track real-time changes in tumor characteristics during treatment. Existing biomarkers (CA15-3 and CEA) for post-treatment monitoring are unsatisfactory. This study explores the clinical validity and stability of thioredoxin1 (Trx1) in a 54-month longitudinal study, reflecting tumor characteristics during treatment. Methods: Approved by IRB from Chungnam National University Hospital (IRB: 2021-02-003). Fourteen out of the initial 20 BC patients were finally enrolled because pre-surgery samples for the 6 patients excluded were missing. A total of 116 sera were collected before and after surgery at intervals from 6 to 54 months. After isolating the serum, an immunoassay was performed to measure the level of serum Trx1 using the DxMe® BC kit (E&S Healthcare). CA15-3 and CEA levels were measured in paired samples and collected from medical records. The results were retrospectively analyzed along with clinical information, and the profile of Trx1 level change was analyzed for each individual. Results: The blood Trx1 levels in pre-operation BC patients were 20.68±4.44 U/ml (±SD). From 6 months’ post-operation to the 54th month, blood Trx1 levels in patients were consistently low, averaging 5.43±3.34 U/ml (p < 0.0001 compared to pre-op). In contrast, levels of CEA and CA15-3 did not change significantly before and after surgery. The pre-op and post-op AUC for Trx1, CA15-3, and CEA were 0.998 (95% CI: 0.941 to 1.000), 0.599 (95% CI: 0.482 to 0.709), and 0.550 (95% CI: 0.433 to 0.663), respectively. There was no significant difference in the decreasing profile of Trx1 levels over 54 months between different treatment methods. While existing a microscopic difference according to BC characteristics, all post-op values were already below the cut-off value. Regardless of treatment, Trx1 levels decreased to those of normal healthy women after surgery. There were no recurring cases to compare over 54 months. Conclusions: The results of this 54-month post-operation tracking observation revealed a rapid decrease in Trx1 levels in the blood after surgery, which remained consistently downregulated without a statistical association with pathological findings. This suggests that Trx1 is related to the presence of tumor masses rather than the pathological characteristics of the tumor. It is likely that if any treatment causes the removal and suppression of BC, the level of Trx1 is kept low. Besides its already reported ability to detect BC in blood, Trx1 levels have the potential to serve as a monitoring biomarker in the management of BC patients after treatment.