Serum 25-hydroxyvitamin D levels in early and advanced breast cancer

Cancer Research UK Laboratories, Department of Cancer Medicine, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, UK.
Journal of Clinical Pathology (Impact Factor: 2.92). 01/2007; 59(12):1334-6. DOI: 10.1136/jcp.2006.042747
Source: PubMed


Laboratory and epidemiological studies have implicated vitamin D deficiency in the pathogenesis of breast cancer. 1,25-Dihydroxyvitamin D (1,25(OH)(2)D) promotes differentiation and apoptosis, and potently inhibits proliferation of malignant breast epithelial cells in culture. Serum levels of 1,25(OH)(2)D are higher in normal women than in patients with primary breast cancer.
To clarify the role of vitamin D in breast cancer progression by comparing the levels of serum vitamin D in patients with early and in those with advanced breast cancer.
Circulating levels of 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH) and calcium were measured prospectively in 279 Caucasian women with invasive breast cancer, 204 women with early-stage disease and 75 women with locally advanced or metastatic disease.
Patients with early-stage breast cancer had significantly higher circulating levels of 25(OH)D (p<0.005) and significantly lower PTH (p<0.001) levels than those with advanced disease. Calcium levels did not differ significantly (p = 0.74).
Serum levels of 25(OH)D are significantly higher in patients with early-stage breast cancer than in those with locally advanced or metastatic disease.

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Available from: Samia I Girgis, Jan 03, 2014
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    • "Their data suggests that suboptimal vitamin D levels were more common in women with advanced stage disease, non Caucasians and those who received RT. Stage is not found as a significant factor for low vitamin D levels in our study, despite the other trial results (Palmieri, 2006 ; Khan, 2010). Lastly, the inhomogeneity of the duration between the systemic treatment and the measuring time of 25-OHD levels may play a role in showing no association between vitamine D deficiency/insufficiency and adjuvant CT in our study. "
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    ABSTRACT: Background: Vitamin D deficiency is a potentially modifiable risk factor that may be targeted for breast cancer (BC) prevention. It may also be related to prognosis after diagnosis and treatment. The aim of our study was to determine the prevalence of vitamin D deficiency as measured by serum 25-hydroxy vitamin D (25-OHD) levels in patients with BC and to evaluate its correlations with life-style and treatments. Materials and methods: This study included 186 patients with stage 0-III BC treated in our breast center between 2010-2013. The correlation between serum baseline 25-OHD levels and supplement usage, age, menopausal status, diabetes mellitus, usage of bisphosphonates, body-mass index (BMI), season, dressing style, administration of systemic treatments and radiotherapy were investigated. The distribution of serum 25-OHD levels was categorized as deficient (<10ng/ ml), insufficient (10-24 ng/ml), and sufficient (25-80 ng/ml). Results: The median age of the patients was 51 years (range: 27-79 years) and 70% of them had deficient/insufficient 25-OHD levels. On univariate analysis, vitamin D deficiency/insufficiency was more common in patients with none or low dose vitamin D supplementation at the baseline, high BMI (≥25), no bisphosphonate usage, and a conservative dressing style. On multivariate analysis, none or low dose vitamin D supplementation, and decreased sun-exposure due to a conservative dressing style were found as independent factors increasing risk of vitamin D deficiency/insufficiency 28.7 (p=0.002) and 13.4 (p=0.003) fold, respectively. Conclusions: The prevalence of serum 25-OHD deficiency/insufficiency is high in our BC survivors. Vitamin D status should be routinely evaluated for all women, especially those with a conservative dressing style, as part of regular preventive care, and they should take supplemental vitamin D.
    Asian Pacific journal of cancer prevention: APJCP 02/2014; 15(3):1357-1362. DOI:10.7314/APJCP.2014.15.3.1357 · 2.51 Impact Factor
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    • "Among the mechanisms suggested for a relationship between sunlight and cancer is the genesis of vitamin D in the skin, resulting from the UV light action. In accordance with this hypothesis, there is evidence that lower 25(OH)D3[1-5] and 1,25(OH)2D3[6,7] serum concentrations are encountered in patients with breast cancer, as compared with women without cancer, as well as in patients with advanced or metastatic disease in comparison with those with early-stage disease [8,9]. In addition, 25(OH)D3 deficiency at diagnosis was related with poor prognosis, evaluated as metastasis-free and overall survival [10]. "
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    ABSTRACT: BACKGROUND: Vitamin D transcriptional effects were linked to tumor growth control, however, the hormone targets were determined in cell cultures exposed to supra physiological concentrations of 1,25(OH)2D3 (50-100nM). Our aim was to evaluate the transcriptional effects of 1,25(OH)2D3 in a more physiological model of breast cancer, consisting of fresh tumor slices exposed to 1,25(OH)2D3 at concentrations that can be attained in vivo. METHODS: Tumor samples from post-menopausal breast cancer patients were sliced and cultured for 24 hours with or without 1,25(OH)2D3 0.5nM or 100nM. Gene expression was analyzed by microarray (SAM paired analysis, FDR<=0.1) or RT-qPCR (p<=0.05, Friedman/Wilcoxon test). Expression of candidate genes was then evaluated in mammary epithelial/breast cancer lineages and cancer associated fibroblasts (CAFs), exposed or not to 1,25(OH)2D3 0.5nM, using RT-qPCR, western blot or immunocytochemistry. RESULTS: 1,25(OH)2D3 0.5nM or 100nM effects were evaluated in five tumor samples by microarray and seven and 136 genes, respectively, were up-regulated. There was an enrichment of genes containing transcription factor binding sites for the vitamin D receptor (VDR) in samples exposed to 1,25(OH)2D3 near physiological concentration. Genes up-modulated by both 1,25(OH)2D3 concentrations were CYP24A1, DPP4, CA2, EFTUD1, TKTL1, KCNK3. Expression of candidate genes was subsequently evaluated in another 16 samples by RT-qPCR and up-regulation of CYP24A1, DPP4 and CA2 by 1,25(OH)2D3 was confirmed. To evaluate whether the transcripitonal targets of 1,25(OH)2D3 0.5nM were restricted to the epithelial or stromal compartments, gene expression was examined in HB4A, C5.4, SKBR3, MDA-MB231, MCF-7 lineages and CAFs, using RT-qPCR. In epithelial cells, there was a clear induction of CYP24A1, CA2, CD14 and IL1RL1. In fibroblasts, in addition to CYP24A1 induction, there was a trend towards up-regulation of CA2, IL1RL1, and DPP4. A higher protein expression of CD14 in epithelial cells and CA2 and DPP4 in CAFs exposed to 1,25(OH)2D3 0.5nM was detected. CONCLUSIONS: In breast cancer specimens a short period of 1,25(OH)2D3 exposure at near physiological concentration modestly activates the hormone transcriptional pathway. Induction of CYP24A1, CA2, DPP4, IL1RL1 expression appears to reflect 1,25(OH)2D3 effects in epithelial as well as stromal cells, however, induction of CD14 expression is likely restricted to the epithelial compartment.
    BMC Cancer 03/2013; 13((1)):119. DOI:10.1186/1471-2407-13-119 · 3.36 Impact Factor
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    • "It has been documented that consumption of oral calcium and serum levels of vitamin D are associated with reduced risk of breast cancer in premenopausal women but the results were not statistically significantly in postmenopausal women.[9] There are data showing that locally advanced breast cancer patients have more severe vitamin D deficiency than those with early stage disease.[10] "
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    ABSTRACT: The aim was to determine serum vitamin D levels in breast cancer patients and to assess its risk association with grade and stage of the tumor. Ninety breast cancer patients and equal number of age-matched healthy females were recruited into the study by consecutive sampling over a period of 6 months for this case control study. Serum 25(OH)2D levels and CT bone mineral density was done. The mean age was 46±1.5 years. Age, marital status, menopausal, residential area, parda observing status, and body mass index were similar in distribution among cases and controls. The mean serum vitamin D level in the breast cancer patients was 9.3 ng/ml and in the control group was 14.9 ng/ml (P value <0.001). Vitamin D deficiency was seen in 95.6% (86) breast cancer patients and in 77% (69) of the control group (P value <0.001). Among the breast cancer patients the tumor characteristics (histology, grade, stage, and receptor status) did not show any significant associations with serum levels of vitamin D. Premenopausal breast cancer females had a mean serum vitamin D level of 10.5 ng/ml and postmenopausal females had a mean value of 13.5 ng/ml (P value 0.015). Low BMD did not correlate significantly with vitamin D deficiency (P value 0.787). Invariably almost all patients with breast cancer were vitamin D deficient. Tumor characteristics did not show any significant associations with serum levels of vitamin D. Bone mineral density did not correlate significantly with vitamin D deficiency.
    05/2012; 16(3):409-13. DOI:10.4103/2230-8210.95684
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