Abstract
Background: Altered copper levels have been observed in several cancers, but studies on the relationship between serum copper and early-stage triple-negative breast cancer (TNBC) remain scare. We sought to establish a predictive model incorporating serum copper levels for individualized survival predictions. Methods: We retrospectively analyzed clinicopathological information and baseline peripheric blood samples of patients diagnosed with early-stage TNBC between September 2005 and October 2016 at Sun Yat-sen University Cancer Center. The optimal cut-off point of serum copper level was determined using maximally selected log-rank statistics. Kaplan-Meier curves were used to estimate survival probabilities. Independent prognostic indicators associated with survival were identified using multivariate Cox regression analysis, and subsequently, prognostic nomograms were established to predict individualized disease-free survival (DFS) and overall survival (OS). The nomograms were validated in a separate cohort of 86 patients from the original randomized clinical trial SYSUCC-001 (SYSUCC-001 cohort). Results: 350 patients were eligible in this study, including 264 in the training cohort and 86 in the SYSUCC-001 cohort. An optimal cut-off value of 21.3 μmol/L of serum copper was determined to maximally divide patients into low- and high-copper groups. After a median follow-up of 87.1 months, patients with high copper levels had significantly worse DFS (p = 0.002) and OS (p < 0.001) than those with low copper levels in the training cohort. Multivariate Cox regression analysis revealed that serum copper level was an independent factor for DFS and OS. Further, prognostic models based on serum copper were established for individualized predictions. These models showed excellent discrimination [C-index for DFS: 0.689, 95% confidence interval (CI): 0.621–0.757; C-index for OS: 0.728, 95% CI: 0.654–0.802] and predictive calibration, and were validated in the SYSUCC-001 cohort. Conclusion: Serum copper level is a potential predictive biomarker for patients with early-stage TNBC. Predictive nomograms based on serum copper might be served as a practical tool for individualized prognostication.
Highlights
Triple-negative breast cancer (TNBC), characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2), is a heterogenic and aggressive subtype of breast cancer
We aimed to explore the relationship between baseline serum copper levels and the survival prognosis of patients with early-stage TNBC in this study, furtherly, we hoped to develop prognostic models combining serum copper levels and clinicopathological factor for individualized survival predictions and personalized decision-making
Patients were eligible for inclusion in this study if they met the following criteria: 1) women with pathologically diagnosed breast cancer without distant metastasis at the time of diagnosis, 2) age ≥18 years old, 3) ER/PR-negative, which was considered as
Summary
Triple-negative breast cancer (TNBC), characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2), is a heterogenic and aggressive subtype of breast cancer. Increased serum copper levels have been associated with disease progression or drug resistance in several malignancies, including advanced breast cancer (Mookerjee et al, 2006; Gupte and Mumper, 2009; Majumder et al, 2009; Kaiafa et al, 2012). These findings suggest that the serum copper level might be served as a biomarker for monitoring tumor progression and treatment efficacy. We sought to establish a predictive model incorporating serum copper levels for individualized survival predictions
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