The effect of various vitamin D supplementation regimens in breast cancer patients

Vitamin D deficiency in the patients treated for breast cancer is associated with numerous adverse effects (bone loss, arthralgia, and falls). The first aim of this study was to assess vitamin D status, determined by 25-OH vitamin D levels, among women diagnosed with breast cancer according to demographic/clinical variables and bone mineral density (BMD). The second aim of this study was to evaluate the effect of daily low-dose and weekly high-dose vitamin D supplementation on 25-OH vitamin D levels. This retrospective study included 224 women diagnosed with stage 0–III breast cancer who received treatment at the James P. Wilmot Cancer Center at the University of Rochester Medical Center. Total 25-OH vitamin D levels (D₂ + D₃) were determined at baseline for all participants. Vitamin D deficiency was defined as a 25-OH vitamin D level < 20 ng/ml, insufficiency as 20–31 ng/ml, and sufficiency as ≥32 ng/ml. BMD was assessed during the period between 3 months before and 6 months following the baseline vitamin D assessment. Based on the participants’ baseline levels, they received either no supplementation, low-dose supplementation (1,000 IU/day), or high-dose supplementation (≥50,000 IU/week), and 25-OH vitamin D was reassessed in the following 8–16 weeks. Approximately 66.5% had deficient/insufficient vitamin D levels at baseline. Deficiency/insufficiency was more common among non-Caucasians, women with later-stage disease, and those who had previously received radiation therapy (P < 0.05). Breast cancer patients with deficient/insufficient 25-OH vitamin D levels had significantly lower lumbar BMD (P = 0.03). Compared to the no-supplementation group, weekly high-dose supplementation significantly increased 25-OH vitamin D levels, while daily low-dose supplementation did not significantly increase levels. Vitamin D deficiency and insufficiency were common among women with breast cancer and associated with reduced BMD in the spine. Clinicians should carefully consider vitamin D supplementation regimens when treating vitamin D deficiency/insufficiency in breast cancer patients.     

Genetic Variations in VDR could Modulate the Efficacy of Vitamin D3 Supplementation on Inflammatory Markers and Total Antioxidant Capacity among Breast Cancer Women: A Randomized Double Blind Controlled Trial

Background: Low levels of vitamin D are found in a great part of breast cancer women. Study subjects using vitaminD3 supplement had lower rates of cancers and fewer markers of inflammation. Additionally, recent studies demonstratethe power of vitamin D supplementation to lower inflammation and oxidative stress biomarkers associate with VDRpolymorphism to reduce inflammation. This study was aimed to assess the impact of vitamin D3 supplementation onthe serum concentration of inflammatory markers and antioxidant capacity with regard to VDR polymorphism in theVDR gene in breast cancer women. Methods: A randomized, double-blind, placebo-controlled trial was conducted on 56breast cancer women. Participants were assigned to 2 treatment arms: placebo and vitamin D3 for 2 months intervention.Supplementation group received 50,000 IU of vitamin weekly. Blood samples were collected at baseline and afterthe intervention to measure the 25(OH) D3, TNF-α, TGF- β and TAC. Genotyping was performed for FokI, BsmI, ApaI,and TaqI polymorphism. Results: After eight weeks supplementation, the intervention group showed a significant increasein the serum concentration of 25(OH) D3 (28±2.6 to 39±3.5; p=0.004 and TAC (48.9±13.3 to 63.5±13.3; p= 0.017).Changes in TNF-α, TGF- β1 were not significant. Serum TAC levels of participants with the TT/Tt, Ff genotypes weremore responsive to supplementation. Conclusions: Supplementation with a vitamin D3 increased the TAC in breastcancer women, although it had no effect on inflammatory markers. Serum TAC in the TT/Tt, Ff were more responsive tovitamin D supplement compared with those with the FF/ff and tt genotypes.     

Plasma 25-hydroxyvitamin D and premenopausal breast cancer risk in a German case-control study

Laboratory and epidemiological data have linked vitamin D to breast cancer prevention. Beside dietary intake, endogenous production of vitamin D substantially contributes to a subject's vitamin D status. Most studies, however, have assessed dietary intake only. Although differential effects of vitamin D on premenopausal and postmenopausal breast cancer have been discussed, this is the first study to investigate the association of plasma 25-hydroxyvitamin D [25(OH)D], as indicator of the overall vitamin D status, with breast cancer risk with restriction to premenopausal women only. We used data of a population-based case-control study comprising 289 cases and 595 matched controls. Information on sociodemographic and breast cancer risk factors was collected by questionnaire and plasma 25(OH)D was measured by enzyme immunoassay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. We observed a significant inverse association between breast cancer risk and plasma 25(OH)D concentrations. Compared with the lowest category (<30 nmol/L), the ORs (95% CI) for the upper categories (30-45, 45-60, >or=60 nmol/L) were 0.68 (0.43-1.07), 0.59 (0.37-0.94) and 0.45 (0.29-0.70), respectively (p(trend) = 0.0006). The association was shown to be nonlinear (p(nonlinearity) = 0.06) in fractional polynomial analysis with a stronger effect in women at low plasma 25(OH)D levels, providing some evidence of a threshold effect (at circa 50 nmol/L). The association was stronger in progesterone receptor negative tumors, with suggestive evidence of effect heterogeneity (p(heterogeneity) = 0.05, case-only model). Our findings support a protective effect of vitamin D for premenopausal breast cancer.     

Synchronized seasonal variations of mammographic breast density and plasma 25-hydroxyvitamin d.

BACKGROUND: Dietary vitamin D has been associated with lower mammographic breast density, a strong biomarker for breast cancer risk. Blood 25-hydroxyvitamin D [25(OH)D] is an integrated measure of vitamin D status (from food, supplements, and sun exposure) and varies with season. Our objective was to assess seasonal variations of breast density and compare such variations, if any, with that of 25(OH)D. METHODS: This cross-sectional study includes 741 premenopausal women recruited at screening mammography. Plasma 25(OH)D at recruitment was measured by RIA. Breast density was evaluated using a computer-assisted method. Seasonal variations were modeled using multivariate linear regression and semi-parametric cubic smoothing splines. RESULTS: Season was strongly associated with 25(OH)D (P < 0.0001). The highest smoothed mean 25(OH)D levels were seen at the end of July (81.5 nmol/L) and the lowest in mid-April (52.4 nmol/L). Breast density showed modest seasonal variations (P = 0.028). The lowest smoothed mean breast density was observed in early December (38.5%) and the highest at the beginning of April (44.3%). When a 4-month lag time was presumed, seasonal variations of breast density appeared to be a mirror image of those of 25(OH)D, and the correlation of daily smoothed estimates of mean breast density and 25(OH)D was negative and strong (r = -0.90). CONCLUSION: In premenopausal women, changes in blood vitamin D seem to be inversely related to changes in breast density with a lag time of about 4 months. This finding encourages further investigation of the possibility that vitamin D could reduce breast density and breast cancer risk.     

Vitamin D and Reduction of Breast Cancer Risk

Vitamin D is important in mammary homeostasis, but the vitamin D signaling pathway is dysregulated in breast cancer epithelial cells. Preclinical and several ecologic and associational studies suggest an inverse relation between vitamin D intake or 25-OH D3 levels and mammary cancer risk, particularly in younger women. However, human correlative and interventional trial results are inconsistent, perhaps due to differences in cohort selection, research methodology, confounding influences, or a small magnitude of effect. Significant risk reduction may require blood 25-OH D3 of >50 ng/mL, a level much higher than that generally observed in Western populations in cohort studies or after low doses of supplements in placebo-controlled intervention trials. Ongoing phase II trials in premenopausal women are designed to achieve levels of 25-OH D3 of ≥50 ng/mL and assess impact on risk biomarkers for breast cancer. These studies will inform design of future cancer incidence trials.     

Postmenopausal breast cancer risk and interactions between body mass index,menopausal hormone therapy use,and vitamin D supplementation: Evidence from the E3N cohort

Experimental studies suggest protective effects of vitamin D on breast carcinogenesis, but epidemiological evidence is not conclusive. Body mass index (BMI) has been shown to modulate the effect of supplementation on the vitamin D status, but its potential influence on the relationship with breast cancer risk has been little studied. We investigated a potential interaction between BMI and vitamin D supplementation on breast cancer risk while considering an already reported interaction between vitamin D supplementation and menopausal hormone therapy (MHT) use. Vitamin D supplementation was prospectively investigated in 57,403 postmenopausal women from the French E3N cohort including 2,482 incident breast cancer cases diagnosed between 1995 and 2008. Multivariable hazard ratios (HR) for primary invasive breast cancer and 95% confidence intervals (CI) were estimated using Cox models. Among MHT ever users, vitamin D supplementation was associated with decreased breast cancer risk, similarly across BMI strata (P_homogeneity = 0.83). Among MHT never users, ever vitamin D supplementation was associated with increased postmenopausal breast cancer risk in women with baseline BMI <25 kg/m² (HR = 1.51, 95% CI: 1.13, 2.02), but not in women with higher BMI (0.98, 95% CI: 0.62, 1.56), P_homogeneity = 0.12. In conclusion, our findings suggest that vitamin D supplementation may reduce the excess breast cancer risk in MHT users, but draw attention on a potential risk in postmenopausal women not exposed to high exogenous or endogenous hormones, i.e. non‐overweight MHT‐non users, especially in the present context of increasing vitamin D supplement use and decreasing MHT use.     

A phase 1B dose escalation trial of Scutellaria barbata (BZL101) for patients with metastatic breast cancer

Vitamin D deficiency and insufficiency may contribute to musculoskeletal symptoms and bone loss observed in women taking aromatase inhibitors (AIs). This study was conducted to determine the prevalence of suboptimal vitamin D levels in women initiating adjuvant letrozole for breast cancer and to determine whether supplementation with 50,000 IU of vitamin D3 weekly could reduce musculoskeletal symptoms and fatigue in women who have suboptimal vitamin D levels. Sixty women about to begin an adjuvant AI were enrolled. Baseline 25OHD levels were obtained, and women completed symptom questionnaires. They were then started on letrozole, along with standard dose calcium and vitamin D. Four weeks later, women with baseline 25OHD levels ≤40 ng/ml started additional vitamin D3 supplementation at 50,000 IU per week for 12 weeks. 25OHD levels were re-assessed at 4, 10, and 16 weeks; the questionnaires were repeated at weeks 4 and 16. At baseline, 63% of women exhibited vitamin D deficiency (<20 ng/ml) or insufficiency (20–31 ng/ml). 25OHD levels >40 ng/ml were achieved in all 42 subjects who received 12 weeks of supplementation with 50,000 IU vitamin D3 weekly, with no adverse effects. After 16 weeks of letrozole, more women with 25OHD levels >66 ng/ml (median level) reported no disability from joint pain than did women with levels <66 ng/ml (52 vs. 19%; P = 0.026). Vitamin D deficiency and insufficiency are prevalent in post-menopausal women initiating adjuvant AI. Vitamin D3 supplementation with 50,000 IU per week is safe, significantly increases 25OHD levels, and may reduce disability from AI-induced arthralgias.     

Circulating 25-Hydroxy Vitamin D Relative to Vitamin D Receptor Polymorphism after Vitamin D3 Supplementation in Breast Cancer Women: A Randomized,Double-Blind Controlled Clinical Trial

Objective: The influence of vitamin D receptor (VDR) genetic variation on serum 25-hydroxyvitamin D levels [25(OH)D] after vitamin D3 supplementation remains unclear. We aimed to investigate changes of 25(OH)D in a randomized, double-blind, placebo-controlled clinical trial, according to VDR genotype, after provision of vitamin D3 to breast cancer cases for a 2-month period. Methods: Participants were assigned to two treatment arms: placebo (n = 28) and vitamin D3 supplementation (n =28). The supplementation group received 50,000 IU of vitamin D every week for 2 months. Blood samples were collected at baseline and after intervention to measure serum 25(OH) D3. Genotypes were assessed for FokI, BsmI, ApaI, and TaqI polymorphisms. Results: After eight weeks supplementation, the rvention group showed a significant increase in the serum concentration of 25(OH) D3 (28±2.6 to 39±3.5; p=0.004). Subjects were then classified into twelve subgroups according to different VDR genotypes. Subjects with ff/Ff, TT/Tt, and Bb genotypes had significantly higher increases in serum 25(OH)D compared to those with FF, tt, and BB/bb genotypes post-intervention. Serum vitamin D3 levels with the AA genotype were lower than with aa/ Aa. No differences were found among other subgroups. Conclusion: Vitamin D3 supplementation increases serum 25(OH)D in women with breast cancer. Serum vitamin D3 in TT/Tt, ff/Ff, and Bb carriers was more responsive to vitamin D supplementation than in those with FF/ff and tt genotypes. Other subgroups might gain less from vitamin D3 supplementation.     

Serum 25-hydroxyvitamin D levels and survival in colorectal and breast cancer patients: Systematic review and meta-analysis of prospective cohort studies

AimTo estimate the association between serum 25-hydroxyvitamin D (25(OH)D) levels and survival among colorectal and breast cancer patients.MethodsWe performed a comprehensive literature search of prospective cohort studies assessing the association of serum 25(OH)D levels with survival in colorectal and breast cancer patients. Study characteristics and results were extracted and dose–response relationships were graphically displayed in a standardised manner. Meta-analyses using random effects models were performed to estimate pooled hazard ratios.ResultsThe systematic search yielded five studies including 2330 colorectal cancer patients and five studies including 4413 breast cancer patients all of which compared mortality across two to five categories of 25(OH)D levels. Among colorectal cancer patients, pooled hazard ratios (95% confidence intervals) comparing highest with lowest categories were 0.71 (0.55–0.91) and 0.65 (0.49–0.86) for overall and disease-specific mortality, respectively. For breast cancer patients, the corresponding pooled estimates were 0.62 (0.49–0.78) and 0.58 (0.38–0.84), respectively. No significant evidence of heterogeneity between studies was observed.ConclusionHigher 25(OH)D levels (>75 nmol/L) were associated with significantly reduced mortality in patients with colorectal and breast cancer. Randomised controlled trials are needed to evaluate whether vitamin D supplementation can improve survival in colorectal and breast cancer patients with low vitamin D status (25(OH)D < 50 nmol/L) at diagnosis and before treatment.     

Vitamin D Levels in Patients with Breast Cancer: Importance of Dressing Style

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 todetermine the prevalence of vitamin D deficiency as measured by serum 25-hydroxy vitamin D (25-OHD) levelsin patients with BC and to evaluate its correlations with life-style and treatments. Materials and Methods: Thisstudy included 186 patients with stage 0-III BC treated in our breast center between 2010-2013. The correlationbetween serum baseline 25-OHD levels and supplement usage, age, menopausal status, diabetes mellitus, usageof bisphosphonates, body-mass index (BMI), season, dressing style, administration of systemic treatments andradiotherapy 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, vitaminD deficiency/insufficiency was more common in patients with none or low dose vitamin D supplementation at thebaseline, 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 stylewere 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 ourBC survivors. Vitamin D status should be routinely evaluated for all women, especially those with a conservativedressing style, as part of regular preventive care, and they should take supplemental vitamin D.     

Association between 25-hydroxyvitamin D concentration and breast cancer risk in an Australian population: an observational case–control study

The objective of this study is to examine the association between vitamin D status and risk of breast cancer in an Australian population of women. The study design is observational case–control study, performed at Westmead Breast Cancer Institute, Westmead Hospital, Sydney, Australia. 214 women newly diagnosed with breast cancer were matched to 852 controls, and their blood samples were tested at the same laboratory between August 2008 and July 2010. Circulating 25-hydroxyvitamin D (25(OH)D) concentration, was defined as sufficient (≥75 nmol/L), insufficient (50–74 nmol/L), deficient (25–49 nmol/L) or severely deficient (<25 nmol/L). The difference in median 25(OH)D concentration between cases and controls was reported, and the Mann–Whitney U test was used to determine the significance of the difference. Odds ratios and 95 % confidence intervals for the risk of breast cancer were estimated by Cox regression. Median plasma 25(OH)D was significantly lower in cases versus controls overall (53.0 vs 62.0 nmol/L, P < 0.001) and during summer (53.0 vs 68.0 nmol/L, P < 0.001) and winter (54.5 vs 63.0 nmol/L, P < 0.001). Median 25(OH)D was also lower in cases when stratified by BMI (<30, ≥30) and age group (<50, ≥50 years) compared to matched controls, although the difference failed to reach statistical significance. In a Cox regression model, plasma 25(OH)D was inversely associated with the odds ratio of breast cancer. Compared to subjects with sufficient 25(OH)D concentration, the odds ratios of breast cancer were 2.3 (95 % CI 1.3–4.3), 2.5 (95 % CI 1.6–3.9) and 2.5 (95 % CI 1.6–3.8) for subjects categorised as severely deficient, deficient or insufficient vitamin D status, respectively. The results of this observational case–control study indicate that a 25(OH)D concentration below 75 nmol/L at diagnosis was associated with a significantly higher risk of breast cancer. These results support previous research which has shown that lower 25(OH)D concentrations are associated with increased risk of breast cancer.     

The determinants of serum vitamin D levels in participants in a melanoma case?Ccontrol study living in a temperate climate

Background

We report the determinants of serum levels of vitamin D in a UK melanoma case?Ccontrol study benefitting from detailed exposure and genotyping data.

Methods

Sun exposure, supplemental vitamin D, and SNPs reported to be associated with serum levels were assessed as predictors of a single serum 25-hydroxyvitamin D₃ measurement adjusted for season, age, sex, and body mass index.

Results

Adjusted analyses showed that vitamin D levels were sub-optimal especially in the sun-sensitive individuals (?2.61?nmol/L, p?=?0.03) and for inheritance of a genetic variant in the GC gene coding for the vitamin D-binding protein (?5.79 for heterozygotes versus wild type, p?=?<0.0001). Higher levels were associated with sun exposure at the weekend in summer (+4.71?nmol/L per tertile, p?=?<0.0001), and on hot holidays (+4.17?nmol/L per tertile, p?=?<0.0001). In smoothed scatter plots, vitamin D levels of 60?nmol/L in the non-sun-sensitive individuals were achieved after an average 6?h/day summer weekend sun exposure but not in the sun-sensitive individuals. Users of supplements had levels on average 11.0?nmol/L higher, p?=?<0.0001, and achieved optimal levels irrespective of sun exposure.

Conclusions

Sun exposure was associated with increased vitamin D levels, but levels more than 60?nmol/L were reached on average only in individuals reporting lengthy exposure (??12?h/weekend). The sun-sensitive individuals did not achieve optimal levels without supplementation, which therefore should be considered for the majority of populations living in a temperate climate and melanoma patients in particular. Inherited variation in genes such as GC is a strong factor, and carriers of variant alleles may therefore require higher levels of supplementation.     

Colonic epithelial cell proliferation decreases with increasing levels of serum 25-hydroxy vitamin D.

Epidemiological evidence suggests a potential role for vitamin D in colon cancer prevention. Vitamin D, absorbed from the intestine or derived from solar ultraviolet light, is metabolized in the liver to 25-hydroxyvitamin D (25-OH D(3)). Previous studies examining effects of vitamin D upon carcinogenesis have focused upon the active metabolite 1,25-dihydroxyvitamin D [1,25-(OH)(2) D(3)], which interacts with nuclear vitamin D receptors in several organs. Until recently, the metabolism of 25-OH D(3) to 1,25-(OH)(2) D(3) was believed to occur only in the kidney, but more recent studies have shown that 25-OH D(3) conversion to 1,25-(OH)(2) D(3) can occur in other tissues. We examined the association between fasting levels of 25-OH D(3), 1,25-(OH)(2) D(3), and BsmI polymorphism of the vitamin D receptor (VDR) gene with indices of colonic epithelial cell proliferation and differentiation in a chemoprevention study, after giving vitamin D or calcium and taking rectal biopsies that were incubated with bromodeoxyuridine. Vitamin D receptor polymorphism was determined by genotyping of the 3' BsmI polymorphism in intron eight of the VDR gene. No significant changes in cell proliferation or in differentiation were found in subjects between study start and end. However, fasting serum levels of 25-OH D(3) showed a highly significant decrease with whole crypt labeling index and the size of the proliferative compartment (phi h). There was no correlation between serum levels of 1,25-(OH)(2) D(3) and the proliferative parameters. Calcium supplementation induced a significant effect upon the relationship between serum 25-OH D(3) and rectal epithelial cell labeling index and phi h when studied by covariance analysis without a relationship with 1,25-(OH)(2) D(3) levels. VDR genotype did not influence the effects of serum 25-OH D(3) or serum 1,25-(OH)(2) D(3) levels upon proliferation. These data suggest that there might be a local effect of 25-OH D(3) on colonic epithelial cells through conversion of 25-OH D(3) to 1,25-(OH)(2) D(3). Subsequent studies have demonstrated the presence of 1alpha-hydroxylase mRNA in normal colorectal epithelium and in colorectal cancer. Thus, vitamin D may have an important role in determining the effects of calcium on colorectal epithelial proliferation and may explain some of the discrepancies found previously in studies that examine the direct role of calcium on the colorectal epithelium.     

Vitamin D Receptor in Breast Cancer Tissues and Its Relation to Estrogen Receptor Alpha (ER-α) Gene Expression and Serum 25-hydroxyvitamin D Levels in Egyptian Breast Cancer Patients: A Case-control Study

IntroductionThis study aimed to explore the role of vitamin D receptor (VDR) in breast cancer tissues and its relation to serum 25-hydroxyvitamin D [25(OH)D] levels and estrogen receptor alpha (ER-α) gene expression in patients with breast cancer.Patients and MethodsCancerous and normal breast tissues from 40 women with breast cancer were analyzed for quantification of VDR levels and ER-α gene expression. The serum levels of 25(OH)D were measured in patients with breast cancer and controls by radioimmunoassay.ResultsPatients with breast cancer had serum levels of 25(OH)D significantly lower than normal control subjects. The levels of VDR and ER-α were significantly higher in breast cancer tissues than in normal breast tissues. The serum levels of 25(OH)D were indirectly and significantly correlated with the tissue levels of both VDR and ER-α gene expression. There was a significant direct correlation between the tissue levels of VDR and ER-α gene expression. The serum 25(OH) D levels, tissue VDR levels, and ER-α gene expression levels were inversely and significantly correlated with breast cancer histopathologic grade. Women with serum 25(OH)D levels ≤ 30 nmol/L, tissue levels of VDR > 5 ng/mL, and tissue levels of ER-α gene expression > 17.7 copies had significantly increased risk for breast cancer incidence.ConclusionWomen with low serum 25(OH)D levels, high tissue levels of VDR, and ER-α gene expression had increased risk for breast cancer. VDR are upregulated in breast cancer tissues thus it may be used for target therapy especially in hormone-negative breast cancer.     

Associations of serum 25-hydroxyvitamin D with overall and breast cancer–specific mortality in a multiethnic cohort of breast cancer survivors

Purpose

Despite limited evidence on the association of vitamin D with outcomes in breast cancer survivors, some clinicians advise breast cancer patients to use vitamin D supplements. More evidence is needed to inform these recommendations.

Methods

In the Health, Eating, Activity, and Lifestyle study, we examined associations of post-treatment serum concentrations of 25-hydroxyvitamin D (25(OH)D) on overall and breast cancer–specific mortality in 585 breast cancer survivors from western Washington State, New Mexico, and Los Angeles County. 25(OH)D was measured in stored blood collected 2 years post-enrollment. Outcomes were ascertained from the Surveillance, Epidemiology, and End Results registries and medical records. Cox proportional hazards models were fit to assess associations of serum 25(OH)D with overall and breast cancer–specific mortality.

Results

After a median follow-up of 9.2 years; 110 women died, including 48 from breast cancer. Standard cut points classified 211 (31.6 %) women as serum 25(OH)D deficient (<20 ng/mL), 189 (32.2 %) as insufficient (20–30 ng/mL), and 185 (36.2 %) as sufficient (>30 ng/mL). Compared to women with deficient 25(OH)D, those in the sufficient ranges had a decreased risk of overall mortality (age-adjusted HR = 0.58; 95 % CI 0.36–0.96); however, multivariate adjustments attenuated the association (HR = 0.90; 95 % CI 0.50–1.61). No association was found between serum 25(OH)D and breast cancer–specific mortality (sufficient: HR = 1.21; 95 % CI 0.52–2.80) in multivariate models.

Conclusion

In this breast cancer cohort, higher serum 25(OH)D may be associated with improved survival, but results were not statistically significant and must be interpreted with caution. The potential prognostic effect of vitamin D from diet, supplements, or both should be evaluated in future larger studies with additional endpoints from breast cancer patients.     

Vitamin D and breast cancer: interpreting current evidence

Preclinical investigations and selected clinical observational studies support an association between higher vitamin D intake and 25-hydroxyvitamin D levels with lower breast cancer risk. However, the recently updated report from the Institute of Medicine concluded that, for cancer and vitamin D, the evidence was 'inconsistent and insufficient to inform nutritional requirements'. Against this background, reports examining vitamin D intake, 25-hydroxyvitamin D levels and breast cancer incidence and outcome were reviewed. Current evidence supports the pursuit of several research questions but not routine 25-hydroxyvitamin D monitoring and vitamin D supplementation to reduce breast cancer incidence or improve breast cancer outcome.     

Evaluation of vitamin D deficiency in breast cancer patients on bisphosphonates

BACKGROUND: Bisphosphonates are very effective in treating osteoporosis and metastatic bone disease; however, unfavorable outcomes can occur when they are given to patients with occult vitamin D deficiency. No clear consensus exists on the assessment of vitamin D status in cancer patients undergoing bisphosphonate therapy. This study examines the prevalence of vitamin D deficiency among breast cancer patients treated with bisphosphonates for osteoporosis or metastatic bone disease, and observes the use of calcium and vitamin D supplementation in these patients. METHODS: This retrospective study reviewed the electronic records of 321 breast cancer patients treated with bisphosphonates. Information on age, race, and serum levels of 25-hydroxyvitamin D (25-OHD), parathyroid hormone, and calcium were collected, and intakes of calcium and vitamin D supplements were queried in an outpatient pharmacy database. RESULTS: Of the 321 patients treated with bisphosphonates, 209 (65.1%) had their 25-OHD levels checked at least once. Of these patients, 57 (27.3%) had a serum 25-OHD level <20 ng/ml. Of the 209 patients with a known 25-OHD level, only eight (3.8%) received >600 IU of vitamin D per day, and 41 (19.6%) patients received 400-600 IU of vitamin D daily. CONCLUSION: Especially in the setting of metastatic bone disease in breast cancer patients, we advocate routine 25-OHD concentration screening for vitamin D deficiency in general. Clear guidelines for the diagnosis of vitamin D deficiency in cancer patients would be extremely beneficial to have, as would identification of the proper dose of vitamin D supplementation. We recommend 1,000 IU daily to our metastatic cancer patients.     

Role of Vitamin D Deficiency and Lack of Sun Exposure in the Incidence of Premenopausal Breast Cancer: a Case Control Study in Sabzevar,Iran

Background: Vitamin D has been suggested as one of the critical factors for female reproductive health withprotective activities against different cancers but there are conflicting facts regarding its role on breast cancerwithout any clear data on premenopausal cases. This study aimed to evaluate the role of vitamin D from dietarysources and sunlight exposure on the incidence of premenopausal breast cancer. Materials and Methods: Weconducted a case control study on 60 newly diagnosed premenopausal breast cancer patients and 116 normalwomen who lived in Sabzevar and surrounding villages in Razavi, Khorasan, a rural and conservative area ofIran. Results: The mean concentrations of 25-OH vitamin D in cases and controls were 15.2±8.15 vs 15.5±7/45ng/ml, both well below normal values elsewhere. In fact 50% of analyzed individuals showed very severe orsevere vitamin D deficiency and the rest (25%) were detected in suboptimal levels. Although the lack of vitaminD and calcium supplementation increased slightly the risk of premenopausal breast cancer (p=0.009, OR=1.115,CI 95%=1.049-1.187), higher prevalence of weekly egg consumption (86.66% vs 96.55%, p=0.023, OR=0.232,CI 95% 0.065-0.806) showed a slight protective role. The last but the most important risk factor was lack ofsunlight exposure because the breast cancer patients had total body coverage from sun (p=0.007, OR=10.131,CI 98% 0.314-78.102). Conclusion: This study pointed out the role of vitamin D and other possible risk factorson the development and growth of breast tumors in this special geographical region. Although this study hasrevealed the interactions between hormonal and environmental factors in this province of Iran, understandingthe deficiency pattern and its contribution to other lifestyle factors elsewhere is also necessary.     

A Pilot Study for a Randomized Controlled Trial to Prevent Gastric Cancer in High-risk Japanese Population: Study Design and Feasibility Evaluation

Observational epidemiological studies suggest that some nutrients reduce the risk of gastric cancer and that individuals with atrophic gastritis are at high risk of developing gastric cancer. One possible measure for gastric cancer prevention is therefore nutritional supplementation for the high risk group. Before recommending this strategy for the general public, however, a randomized controlled trial (RCT) is necessary. To evaluate the feasibility of an RCT, the authors conducted a pilot study using recipients of a health check-up program in a general hospital in Japan. The subjects who were asked to participate in the trial had been diagnosed as having atrophic gastritis on the basis of serum pepsinogen I <70 ng/ml and the ratio of pepsinogen I to II <3.0. They were requested to ingest double-blinded capsules containing different levels of vitamin C and β-carotene every day. Out of the 219 subjects (118 males, 101 females) who were eligible for the study and had the required pepsinogen measurement, 90 (41%) met the criteria for atrophic gastritis. Among them, 55 (61%) (35 males, 20 females) gave their informed consent to participate in the RCT. Fifty-four participants completed a 3-month course of supplementation, and all of them agreed to a 5-year supplementation period. The authors concluded that an RCT using double-blinded nutritional supplements and targeting apparently healthy individuals is feasible in an intervention study for cancer prevention in Japan.