Establishment and Validation of Prognostic Nomograms Based on Serum Copper Level for Patients With Early-Stage Triple-Negative Breast Cancer

Fangfang Duan; Jianpei Li; Jiajia Huang; Xin Hua; Chenge Song; Li Wang; Xiwen Bi; Wen Xia; Zhongyu Yuan

doi:10.3389/fcell.2021.770115

Establishment and Validation of Prognostic Nomograms Based on Serum Copper Level for Patients With Early-Stage Triple-Negative Breast Cancer

Front Cell Dev Biol. 2021 Nov 25:9:770115. doi: 10.3389/fcell.2021.770115. eCollection 2021.

Authors

Fangfang Duan¹, Jianpei Li², Jiajia Huang¹, Xin Hua¹, Chenge Song¹, Li Wang¹, Xiwen Bi¹, Wen Xia¹, Zhongyu Yuan¹

Affiliations

¹ Departments of Medical Oncology, The State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
² Departments of Clinical Laboratory Medicine, The State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.

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.

Keywords: early-stage triple-negative breast cancer; maximally selected log-rank statistics; prognostic nomograms; serum copper level; survival.