Abstract
The dysregulation of iron homeostasis has been explored in malignancies. However, studies focusing on the association between the serum iron level and prognosis of patients with early-stage triple-negative breast cancer (TNBC) are scarce. Accordingly, in current study, 272 patients with early-stage TNBC treated at Sun Yat-sen University Cancer Center (SYSUCC) between September 2005 and October 2016 were included as a training cohort, another 86 patients from a previous randomized trial, SYSUCC-001, were analyzed as a validation cohort (SYSUCC-001 cohort). We retrospectively collected their clinicopathological data and tested the serum iron level using blood samples at the diagnosis. In the training cohort, patients were divided into low-iron and high-iron groups according to the serum iron level cut-off of 17.84 μmol/L determined by maximally selected rank statistics. After a median follow-up of 87.10 months, patients with a low iron had a significantly longer median disease-free survival (DFS) of 89.13 [interquartile range (IQR): 66.88–117.38] months and median overall survival (OS) of 92.85 (IQR: 68.83–117.38) months than those in the high-iron group (median DFS: 75.25, IQR: 39.76–105.70 months, P = 0.015; median OS: 77.17, IQR: 59.38–110.28 months, P = 0.015). Univariate and multivariate Cox analysis demonstrated the serum iron level to be an independent predictor for DFS and OS. Then, a prognostic nomogram incorporating the serum iron level, T stage and N stage was developed for individualized prognosis predictions. It had good discriminative ability with a C-index of DFS (0.729; 95% CI 0.666–0.792) and OS (0.739; 95% CI 0.666–0.812), respectively. Furtherly, we validated the predictive model in the SYSUCC-001 cohort, which also showed excellent predictive performance with a C-index of DFS (0.735; 95% CI 0.614–0.855) and OS (0.722; 95% CI 0.577–0.867), respectively. All these suggested that the serum iron level might be a potential prognostic biomarker for patients with early-stage TNBC, the predictive model based on it might be served as a practical tool for individualized survival predictions.
Highlights
MATERIALS AND METHODSTriple-negative breast cancer (TNBC), lacking the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2), accounts for about 10–15% and is the most aggressive molecular subtype of all breast tumors (Sung et al, 2021; Wang et al, 2021)
Early relapse, strong heterogeneity and limited therapeutic options, triple-negative breast cancer (TNBC) patients usually have distant metastasis at the diagnosis and worse long-term clinical outcomes compared with patients with other subtypes of breast cancer (Gadi and Davidson, 2017; Vagia et al, 2020)
We retrospectively analyzed the prognostic value of the serum iron level in women newly diagnosed with TNBC between September 2005 and October 2016 at Sun Yat-sen University Cancer Center (SYSUCC) in Guangzhou, China
Summary
MATERIALS AND METHODSTriple-negative breast cancer (TNBC), lacking the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2), accounts for about 10–15% and is the most aggressive molecular subtype of all breast tumors (Sung et al, 2021; Wang et al, 2021). Early relapse, strong heterogeneity and limited therapeutic options, TNBC patients usually have distant metastasis at the diagnosis and worse long-term clinical outcomes compared with patients with other subtypes of breast cancer (Gadi and Davidson, 2017; Vagia et al, 2020). Iron is involved in cell respiration, oxygen transport, energy metabolism, DNA repair, and different signaling pathways (Torti et al, 2018). It is essential for human health, but excess iron or iron overload due to disorders of iron metabolism can induce severe toxicity even tumorigenesis in humans (Wu et al, 2004; Adams, 2015)
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