Supplementary Material for: Clinical Prognostic Significance of LRG1 in Metastatic Breast Cancer

Background & objective: Leucine-rich α-2 glycoprotein 1 (LRG1) is a multifunctional pro-inflammatory signaling molecule that has been proposed as a promising biomarker and potential therapeutic target across various types of cancer. Prospective studies investigating LRG1 in breast cancer patients are scarce. The purpose of this study was to investigate whether circulating LRG1 levels are associated with overall survival in patients with metastatic breast cancer. Methods: The present study encompassed 47 individuals with ER-positive/HER2-negative metastatic breast cancer who were scheduled to receive treatment with CDK4/6 inhibitors in combination with endocrine therapy as a first or second line of treatment. The primary endpoint was three-year overall survival. Plasma LRG1 levels were measured using an enzyme-linked immunosorbent assay. Results: LRG1 levels were significantly associated with advanced age, C-reactive protein, invasive lobular carcinoma, and the presence of lung metastases. During the three-year follow-up period, 30% of participants died. Kaplan–Meier analysis based on the optimal cutoff indicated that patients with elevated LRG1 levels had a significantly higher risk of mortality compared to those with lower concentrations (log-rank p = 0.008), with a hazard ratio (HR) of 3.22 [95% CI: 1.32–11.05]; P = 0.013. This association remained significant after adjustment for potential confounders. Similarly, when modeled as a log₂-transformed continuous variable, LRG1 levels were also significantly associated with overall survival (HR per doubling = 5.82 [95% CI: 1.35–25.13]; P = 0.018). Conclusions: LRG1 significantly predicted three-year overall survival in patients with metastatic breast cancer, supporting its potential as a prognostic biomarker.