Abstract
BackgroundA higher vitamin D intake improves the prognosis of early stage breast cancer (BC) patients. We hypothesized that vitamin D intake should refer to vitamin D receptor (VDR) expression. In order to prove this hypothesis, we first intend to evaluate the correlation between VDR expression and prognosis of BC patients using meta-analysis.MethodsLiteratures from PubMed, Embase, and the Cochrane Library (last update by May 20, 2020) were retrieved to find studies assessing the prognostic role of VDR in BC. The hazard ratios (HRs) for patients’ survival were extracted for pooled analyses. Subgroup analysis, sensitivity analysis and meta-regression were performed to explore the sources of heterogeneity.ResultsSeven articles containing eight studies with 2503 patients were enrolled. The results from the pooled analyses showed that the VDR expression generally had no relationship with BC patients’ overall survival (OS), disease-free survival (DFS), cancer-specific survival (CSS), and progression-free survival (PFS) (P > 0.05). Because only the number of studies exploring the relationship between VDR expression and OS is greater than five and there is heterogeneity, we explored the sources of heterogeneity of these studies. Subgroup analyses showed that the VDR expression in the nucleus had no relationship with OS, but high total VDR expression in the nucleus and cytoplasm was related to a better OS (pooled HR = 0.41; 95% CI = 0.18–0.95; P = 0.038). In addition, in subgroup of studies using cut-off values other than ‘immunoreactive score (IRS)>5’ and ‘IRS > 25′, high VDR expression was associated with a better OS (pooled HR = 0.47; 95% CI = 0.30–0.74; P = 0.001). Sensitivity analysis showed that the result pattern was not obviously affected by any single study. Meta-regression showed that the source of heterogeneity was not country (P = 0.657), pathological type (P = 0.614), molecular type (P = 0.423), staining location (P = 0.481), or cut-off value (P = 0.509).ConclusionsThe protein expression level of VDR in entire BC cells evaluated by immunohistochemistry is related to the OS of BC patients. It is expected that a more individualized vitamin D intake and a more accurate prognosis assessment can be recommended for BC patients based on the VDR expression. Of course, more preclinical and clinical studies are needed.
Highlights
A higher vitamin D intake improves the prognosis of early stage breast cancer (BC) patients
The protein expression level of vitamin D receptor (VDR) in entire BC cells evaluated by immunohistochemistry is related to the overall survival (OS) of BC patients
It is expected that a more individualized vitamin D intake and a more accurate prognosis assessment can be recommended for BC patients based on the VDR expression
Summary
A higher vitamin D intake improves the prognosis of early stage breast cancer (BC) patients. In order to prove this hypothesis, we first intend to evaluate the correlation between VDR expression and prognosis of BC patients using meta-analysis. Findings from a prospective study including 10,578 premenopausal and 20,909 postmenopausal women suggested that higher intakes of calcium and vitamin D may reduce the risk of BC in premenopausal women [11]. We established a scientific hypothesis that the vitamin D intakes of BC patients should refer to their VDR expression levels. To prove this hypothesis, we first need to verify the correlation between the VDR expression and the prognosis of BC patients
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