The Association Between Breast Cancer Prognostic Indicators and Serum 25-OH Vitamin D Levels

Department of Radiation Oncology, University of Rochester Medical Center, Rochester, New York, NY, USA.
Annals of Surgical Oncology (Impact Factor: 3.93). 03/2012; 19(8):2590-9. DOI: 10.1245/s10434-012-2297-3
Source: PubMed


Studies show that women with low vitamin D levels have an increased risk of breast cancer (BC) incidence and mortality, but there is a lack of research examining vitamin D levels and prognostic variables in BC patients. The aim of this study is to examine 25-OH vitamin D levels between BC cases and controls and by prognostic indicators among BC cases.
25-OH vitamin D levels were collected from 194 women who underwent BC surgery and 194 cancer-free (CF) controls at the University of Rochester between January 2009 and October 2010. Mean 25-OH vitamin D levels and odds ratios (OR) were calculated by case/control status for the overall cohort and by prognostic indicators (invasiveness, ER status, triple-negative status, Oncotype DX score, molecular phenotype) for BC cases.
BC cases had significantly lower 25-OH vitamin D levels than CF controls (BC: 32.7 ng/mL vs. CF: 37.4 ng/mL; P = .02). In case-series analyses, women with suboptimal 25-OH vitamin D concentrations (<32 ng/mL) had significantly higher odds of having ER- (OR = 2.59, 95% confidence interval [95% CI] = 1.08-6.23) and triple-negative cancer (OR = 3.15, 95% CI = 1.05-9.49) than those with optimal 25-OH D concentrations. Women with basal-like phenotype had lower 25-OH vitamin D levels than women luminal A phenotype (basal-like: 24.2 ng/mL vs. luminal A: 32.8 ng/mL; P = 0.04).
BC patients with a more aggressive molecular phenotype (basal-like) and worse prognostic indicators (ER- and triple-negative) had lower mean 25-OH vitamin D levels. Further research is needed to elucidate the biological relationship between vitamin D and BC progression.

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    • "The limited epidemiologic data that has been stratified by subtype is mixed - one study reported that the relationship between serum 25(OH)D and reduced risk of breast cancer was strongest for high grade, ER negative or triple negative cancers (Yao and Ambrosone, 2013) whereas another found that low serum 25(OH)D was associated with poor prognosis only in women with the luminal subtype of breast cancer (Kim et al., 2011). It should be noted that while vitamin D deficiency is common in all breast cancer patient populations, it is particularly prevalent in those with triple negative/basal-like tumors, the most aggressive form of the disease (Rainville et al., 2009; Peppone et al., 2012; Yao and Ambrosone, 2013). Even without rigorous “proof” of a beneficial effect of supplemental vitamin D on breast cancer, correction of vitamin D deficiency in women at risk for, or living with, breast cancer should be standard practice. "
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    ABSTRACT: Nuclear receptors exert profound effects on mammary gland physiology and have complex roles in the etiology of breast cancer. In addition to receptors for classic steroid hormones such as estrogen and progesterone, the nuclear vitamin D receptor (VDR) interacts with its ligand 1α,25(OH)2D3 to modulate the normal mammary epithelial cell genome and subsequent phenotype. Observational studies suggest that vitamin D deficiency is common in breast cancer patients and that low vitamin D status enhances the risk for disease development or progression. Genomic profiling has characterized many 1α,25(OH)2D3 responsive targets in normal mammary cells and in breast cancers, providing insight into the molecular actions of 1α,25(OH)2D3 and the VDR in regulation of cell cycle, apoptosis, and differentiation. New areas of emphasis include regulation of tumor metabolism and innate immune responses. However, the role of VDR in individual cell types (i.e., epithelial, adipose, fibroblast, endothelial, immune) of normal and tumor tissues remains to be clarified. Furthermore, the mechanisms by which VDR integrates signaling between diverse cell types and controls soluble signals and paracrine pathways in the tissue/tumor microenvironment remain to be defined. Model systems of carcinogenesis have provided evidence that both VDR expression and 1α,25(OH)2D3 actions change with transformation but clinical data regarding vitamin D responsiveness of established tumors is limited and inconclusive. Because breast cancer is heterogeneous, analysis of VDR actions in specific molecular subtypes of the disease may help to clarify the conflicting data. The expanded use of genomic, proteomic and metabolomic approaches on a diverse array of in vitro and in vivo model systems is clearly warranted to comprehensively understand the network of vitamin D regulated pathways in the context of breast cancer.
    Frontiers in Physiology 06/2014; 5:213. DOI:10.3389/fphys.2014.00213 · 3.53 Impact Factor
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    • "The effect of sunlight exposure on the prognosis of patients with cancer is related to the conversion of vitamin D. Many studies reported that the adequate vitamin D level and more sunlight exposure decreased the incidence and mortality of breast cancer. In additon, it was reported that there was a relationship between low level of vitamin D and more aggresive breast cancer subtypes, especially TNBC (Rainville et al., 2009; Peppone et al., 2012; Yao et al., 2012). It was alsoreported that patients with TNBC had lower vitamin D level, and probably low level of vitamin D may be a characteristic of TBNC. "
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    ABSTRACT: Unlabelled: INTRADUCTION: There is known to be a relationship between vitamin D level and more aggresive breast cancer subtypes, especially triple-negative breast cancer (TNBC). It was reported that sunlight exposure has an effect on the prognosis of patients with cancer, possibly related to the conversion of vitamin D to its active form with sunlight. We aimed to evaluate the effect of sunlight exposure on patients with TNBC. Materials-methods: A total of 1,167 patients with breast cancer from two different regions of Turkey (Antalya and Kayseri, regions having different climate and sunlight exposure intensity over the year) were analysed retrospectively. The ratio of patients with TNBC was identified in those two regions. Results: The ratio of patients with TNBC was 8% and 12% for Kayseri and Antalya regions, respectively, and this difference between the two groups was statistically significant (p=0.021). Discussion: Sunlight exposure may be associated with more prevalent TNBC. This finding should be investigated with a prospective study.
    Asian Pacific journal of cancer prevention: APJCP 02/2013; 14(2):801-3. DOI:10.7314/APJCP.2013.14.2.801 · 2.51 Impact Factor
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    • "Additional evidence is provided by an inverse association between the circulating levels of 25-hydroxyvitamin D3 (the inactive circulating form of vitamin D, which is used to measure the levels of vitamin D in the blood stream) and the risk for developing breast cancer, suggesting that high levels of 25-hydroxyvitamin D3 may be associated with a reduced risk of breast cancer [14]. Furthermore, it has been described that patients with the most aggressive type of breast cancer (triple-negative and basal-like) display the lowest levels of 25-hydroxyvitamin D3 [15,16]. These results are supported by a recent study where it was observed that breast cancer patients with suboptimal vitamin D levels are more likely to have tumours with aggressive profiles and worse prognostic markers [17]. "
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    ABSTRACT: Breast cancer is a heterogeneous disease associated with diverse biological behaviours and clinical outcome. Although some molecular subgroups of breast cancer have a targeted therapy, the most aggressive tumours still lack a molecular target. Despite vitamin D being classically associated with the physiological role of calcium regulation and phosphate transport in bone metabolism, several studies have demonstrated a wide range of functions for this hormone, which are particularly important in the field of cancer. The mechanisms underlying the protective actions of vitamin D in cancer development are only sparsely understood, but evidence shows that vitamin D participates in cell growth regulation, apoptosis and cell differentiation. In addition, it has been implicated in the suppression of cancer cell invasion, angiogenesis and metastasis. Most of vitamin D biological actions are mediated by the vitamin D receptor and the synthesis and catabolism of this hormone are regulated by the enzymes CYP27B1 and CYP24A1. In the present review we highlight research data concerning the function of this hormone in the mammary gland, with a special focus on breast carcinogenesis. Hence, and although the available data are controversial, we consider not only updated information on the epidemiology of vitamin D in breast cancer and its potential value as a therapeutic agent or prophylactic (with an emphasis on molecular mechanisms and effectors of vitamin D action), but include data on its role in other stages of breast cancer progression as well. Accordingly, we review data on the influence of vitamin D in the development of normal breast and the expression of vitamin D-related proteins (VDR, CYP27B1 and CYP24A21) in benign mammary lesions and ductal carcinomas in situ.
    Breast cancer research: BCR 05/2012; 14(3):211. DOI:10.1186/bcr3178 · 5.49 Impact Factor
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