Prognostic value of vitamin D receptor and insulin-like growth factor receptor 1 expression in triple-negative breast cancer

Šoljić, Martina; Mrklić, Ivana; Tomić, Snježana; Omrcen, Tomislav; Šutalo, Nikica; Bevanda, Milenko; Vrdoljak, Eduard

doi:10.1136/jclinpath-2016-204222

Cited by 19 publications

(16 citation statements)

References 34 publications

(10 reference statements)

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“…It is well known that patients with same TNM staging may have different prognosis. Therefore, an effective biological indicator is urgently needed to help assess the prognosis of BC patients [ 20 ]. Although serum vitamin D level and VDR expression are both related to the prognosis of BC patients [ 7 , 11 ], VDR expression seems a more suitable prognostic indicator of BC because serum vitamin D level fluctuates greatly due to diet and sunlight exposure.…”

Section: Discussionmentioning

confidence: 99%

Prognostic role of vitamin D receptor in breast cancer: a systematic review and meta-analysis

Liu

Shi

et al. 2020

BMC Cancer

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Background A 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. Methods Literatures 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. Results Seven 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). Conclusions The 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.

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Section: Discussionmentioning

confidence: 99%

Prognostic role of vitamin D receptor in breast cancer: a systematic review and meta-analysis

Liu

Shi

et al. 2020

BMC Cancer

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“…Insulin-like growth factor receptor 1 (IGFR) is considered as a potential target in cancer therapy (reviewed in [59]). Soljic et al, correlated VDR and IGFR expression with clinico-pathological characteristics of TNBC patients [60]. They observed a positive VDR immunostaining in 27% of cases that negatively correlated with mitotic score, histological grade and a higher proliferation index, evaluated by the expression of Ki-67 and increased overall survival (OS).…”

Section: Observational Studiesmentioning

confidence: 99%

Vitamin D in Triple-Negative and BRCA1-Deficient Breast Cancer—Implications for Pathogenesis and Therapy

Błasiak

Pawłowska

Chojnacki

et al. 2020

IJMS

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Several studies show that triple-negative breast cancer (TNBC) patients have the lowest vitamin D concentration among all breast cancer types, suggesting that this vitamin may induce a protective effect against TNBC. This effect of the active metabolite of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D), can be attributed to its potential to modulate proliferation, differentiation, apoptosis, inflammation, angiogenesis, invasion and metastasis and is supported by many in vitro and animal studies, but its exact mechanism is poorly known. In a fraction of TNBCs that harbor mutations that cause the loss of function of the DNA repair-associated breast cancer type 1 susceptibility (BRCA1) gene, 1,25(OH)2D may induce protective effects by activating its receptor and inactivating cathepsin L-mediated degradation of tumor protein P53 binding protein 1 (TP53BP1), preventing deficiency in DNA double-strand break repair and contributing to genome stability. Similar effects can be induced by the interaction of 1,25(OH)2D with proteins of the growth arrest and DNA damage-inducible 45 (GADD45) family. Further studies on TNBC cell lines with exact molecular characteristics and clinical trials with well-defined cases are needed to determine the mechanism of action of vitamin D in TNBC to assess its preventive and therapeutic potential.

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“…To our knowledge, only one study has assessed VDR expression in all the different molecular subtypes of HBC [ 27 ]. However, in several studies, the expression of VDR in TNBC has been reported, indicating that about 27–40 % of TNBCs express VDR [ 27 , 31 , 32 ], and suggesting the possibility of using the VDR as a therapeutic target against TNBCs.…”

Section: Introductionmentioning

confidence: 99%

Vitamin D receptor (VDR) expression in different molecular subtypes of canine mammary carcinoma

et al. 2021

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Background The molecular-based classification of canine mammary carcinomas (CMCs) has been the focus of much current research. Both in canines and humans, the triple-negative (TN) molecular subtype of mammary cancer is defined by a lack of expression of progesterone receptor (PR), oestrogen receptor (ER) and HER2. It has a poor prognosis; no effective targeted therapy is available. Vitamin D displays anticarcinogenic properties, and the expression of its receptor (VDR) has been found in different molecular subtypes, being about 30–40 % of TN breast cancer (TNBC) positive to it. We assessed the VDR expression in the different molecular subtypes of 58 CMCs from 45 female dogs using an immunohistochemical panel for the molecular classification of included: PR, ER, HER2, cytokeratin (CK) 5, CK14, and Ki67. In addition, we studied the relationship among the molecular subtypes of CMCs and clinicopathologic parameters. Results Investigation showed VDR positivity in 45.0 % of the triple-negative CMCs (TNCMCs), 27.3 % of luminal B and 19.0 % of luminal A. Luminal A was the most molecular subtype represented of the total tumours (36.2 %), followed of TNCMCs (34.5 %), luminal B (20.7 %) and HER2-overexpression (10.3 %). Both HER2-overexpression and TNCMC subtypes were positively related to lymphatic invasion (P = 0.028), simple histologic subtype (P = 0.007), a higher histological grade (P = 0.045) and a trend to higher proliferation index (P = 0.09). Conclusions The highest VDR expression was observed in TNCMC, being almost half of them (45 %) positive to this receptor. VDR expression was absent in HER2-overexpression tumours and low in luminal A and B molecular subtypes.

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Prognostic value of vitamin D receptor and insulin-like growth factor receptor 1 expression in triple-negative breast cancer

Cited by 19 publications

References 34 publications

Prognostic role of vitamin D receptor in breast cancer: a systematic review and meta-analysis

Prognostic role of vitamin D receptor in breast cancer: a systematic review and meta-analysis

Vitamin D in Triple-Negative and BRCA1-Deficient Breast Cancer—Implications for Pathogenesis and Therapy

Vitamin D receptor (VDR) expression in different molecular subtypes of canine mammary carcinoma

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