Diagnostic, prognostic, and treatment monitoring value of plasma X in patients with metastatic breast cancer.

Abstract

37 Background: Metastasis is the main course of death in breast cancer (BC) patients. Reliable prognostic markers are very much appreciated to evaluate possible outcome of patients. Circulating tumor cells (CTC) is a circulating prognostic tumor marker of metastatic breast cancer patients. Despite the big technical challenges in CTC detection, the reliability of CTC enumeration for the prognosis of BC is still on debate. Some studies have proved that the plasma level of X, a major component in extracellular matrix, was increased in patients with metastatic breast cancer. However, the association between the plasma X level and the prognosis of metastatic breast cancer is still unknown. Methods: Plasma X was measured by ELISA in 60 healthy controls, 48 primary breast cancer (PBC) patients, and 212 metastatic breast cancer (MBC) patients. Progression free survival (PFS) and overall survival (OS) were analyzed. An independent cohort with 210 primary and 69 patients with metastatic breast cancer were further investigated to validate our findings. Results: A 2-fold elevation was presented in MBC patients when compared with PBC patients and controls, regardless of their CTC status. A multivariate Cox regression demonstrated that lower X level at base line was associated with longer PFS (HR: 2.50, 95% CI: 1.72–3.63, p = 1.607 × 10-6), as well as longer OS (HR: 3.74, 95% CI: 1.65 – 8.51, p = 0.002). After 1stcycle of chemotherapy, plasma X level was still prognostic and was dramatically decreased in patients who had responded to the treatment (54%, IQR: 36%–64%). In the independent validation round, a 2-fold increase of plasma X was observed again in MBC patients, compared with PBC patients. The prognostic value was also validated for PFS (HR: 2.12, 95% CI: 1.43– 3.84, p = 0.001) and OS (HR: 2.91, 95% CI: 1.73–7.65, p = 0.002) in MBC patients. Conclusions: Plasma X could be used as a diagnostic and prognostic marker for metastatic breast cancer. Its reduction after 1st cycle of chemotherapy could be an indicator of treatment efficacy. This finding may further prevent unnecessary systemic therapy by facilitating personalized medicine in the treatment of metastatic breast cancer.