Vit D and breast cancer bone metastases  Cancer Jan 2010
Vitamin D supplementation counteracts side effect of treatment for bone metastases
Last updated: January 25, 2010
http://digg.com/d31GnHD     Breast cancer trial results
Publication:
    Cancer, January 2010
Study name:
    A phase 2 trial exploring the effects of high-dose (10,000 IU/day) vitamin D3 in breast cancer patients with bone metastases
The results of a phase 2 trial of vitamin D supplementation in women with Stage IV breast cancer have been reported. Vitamin D deficiency has been found to be associated with breast cancer development and progression, and has also been reported in conjunction with increased toxicity from bisphosphonate therapy. Bisphosphonates, which are also used to treat osteoporosis, are used to treat bone metastases in advanced breast cancer patients. The optimal dose of vitamin D supplementation has not been established, however it is possible to obtain the equivalent of a 10,000-IU dose of vitamin D3 from daily sunlight exposure. The study was designed to assess the effect of this dose of vitamin D3 in 40 breast cancer patients with bone metastases who were being treated with bisphosphonates. Participants received daily supplements consisting of 10,000 IU of vitamin D3 and 1000 mg of calcium for four months.
The supplementation regimen was not found to influence bone resorption, nor did it reduce pain overall. However, a reduction in the number of pain sites was observed. Daily doses of 10,000 IU vitamin D3 for four months were found to be safe in patients without conditions causing hypersensitivity to vitamin D. Furthermore, treatment reduced elevated parathyroid hormone levels, which presumably had been caused by long-term bisphosphonate use. However, there did not appear to be a significant palliative benefit nor any significant change in bone resorption.
Vitamin D reduces risk of breast cancer and inhibits progression
The researchers were able to report that supplementation with 10,000 IU of vitamin D daily was generally safe in women with stage IV breast cancer with bone metastases, and that it reduced parathyroid hormone levels that had been increased by bisphosphonate treatment. However, the results with respect to pain relief and bone resorption were no doubt disappointing. While vitamin D deficiency is associated with increased risk of breast cancer, administering vitamin D after breast cancer has progressed to stage IV may be ineffective in slowing disease progression. On the other hand, having established the safety of such as regimen, researchers may be in a position to develop a vitamin D-based treatment that is more effective.
Selected studies
A phase 2 trial exploring the effects of high-dose (10,000 IU/day) vitamin D3 in breast cancer patients with bone metastases Cancer, January 2010
The present report describes the results of a single-arm phase 2 trial of vitamin D supplementation in women with Stage IV breast cancer. Vitamin D deficiency has potential roles in breast cancer development and progression. Vitamin D deficiency has also been reported in conjunction with increased toxicity from bisphosphonate therapy. Bisphosphonates, which are also used to treat osteoporosis, are used to treat bone metastases in advanced breast cancer patients. The optimal dose of vitamin D supplementation has not been established, however daily sunlight exposure can generate the equivalent of a 10,000-IU oral dose of vitamin D3. The study was designed to assess the effects of this dose of vitamin D3 in breast cancer patients with bone metastases. The study included 40 women with bone metastases treated with bisphosphonates. Participants received daily supplements consisting of 10,000 IU of vitamin D3 and 1000 mg of calcium for four months. The effect of this treatment on palliation, calcium metabolism, bone resorption markers, and toxicity were evaluated monthly and compared to baseline. No significant changes in bone resorption markers were observed as a result of the supplementation and there were no changes in global pain scales. However, a significant reduction in the number of sites of pain was observed. A small but statistically significant increase in serum calcium was also found, as was a significant reduction in serum parathyroid hormone. The treatment uncovered two cases of primary hyperparathyroidism, but was not associated with direct toxicity. The authors conclude that daily doses of 10,000 IU vitamin D3 for four months appear safe in patients without comorbid conditions causing hypersensitivity to vitamin D. Furthermore, treatment reduced elevated parathyroid hormone levels, which presumably had been caused by long-term bisphosphonate use. However, there did not appear to be a significant palliative benefit nor any significant change in bone resorption.
Meta-analysis of vitamin D, calcium and the prevention of breast cancer Breast Cancer Research and Treatment, October 2009
The current meta-analysis was designed to investigate the overall effects of vitamin D intake, circulating 25(OH)D vitamin D and 1alpha,25(OH)(2)D vitamin D levels, and calcium intake on the risk of breast cancer. The analysis included data from 11 studies concerning vitamin D intake, seven studies on circulating 25(OH)D, three studies of circulating 1alpha,25(OH)(2)D, and 15 studies concerning calcium intake and risk of breast cancer. A significant inverse relationship was found in the meta-analysis between vitamin D intake and risk of breast cancer, with an overall relative risk (RR) of high compared to low vitamin D intake of 0.91 (95% confidence interval (CI) = 0.85 - 0.97). The highest quantile of circulating 25(OH)D was associated with 45% lower breast cancer risk when compared with the lowest quantile (OR = 0.55, 95% CI = 0.38 - 0.80) . No significant association between the circulating 1alpha,25(OH)(2)D levels and breast cancer was observed (OR = 0.99, 95% CI = 0.68 - 1.44). With respect to calcium, a 19% decrease in risk of breast cancer was found for those with the highest quantile of calcium consumption compared to the lowest quantile (RR = 0.81, 95% CI = 0.72 - 0.90). The authors conclude that the results provide strong evidence that vitamin D and calcium have a chemopreventive effect against breast cancer.
The effect of high-dose vitamin D supplementation on 25-OH vitamin D levels in breast cancer patients during treatment American Society of Clinical Oncology Breast Cancer Symposium, October 2009
The present study was designed to determine the prevalence of vitamin D deficiency among breast cancer patients and to investigate the impact of high-dose vitamin D supplementation on circulating vitamin D levels in these patients. Vitamin D deficiency has been found to be associated with low bone mineral density and heightened breast cancer incidence, recurrence, and mortality. Adjuvant hormonal therapy reduces bone mineral density and increases fracture risk. The study included approximately 166 women from whom serum 25-OH vitamin D levels were obtained and 28 women aged 30 to 88 undergoing treatment (hormonal therapy, radiation, chemotherapy, or any combination) for non-metastatic breast cancer for whom bone mineral density was also measured. Vitamin D deficiency was assessed for the total study group at baseline, and compared with respect to race and stage of breast cancer. Vitamin D and bone mineral density were compared while controlling for bisphosphonate use, age, race, stage of disease and season of year at baseline. Vitamin D deficient patients were given weekly, high-dose vitamin D (at least 50,000 IU) and plasma vitamin D levels were compared at three different supplementation levels. The average baseline 25-OH vitamin D level of breast cancer patients was only 26.9 ng/ml; approximately 69% of the patients were considered deficient (defined as 25-OH vitamin D levels under 32 ng/mL). Significantly lower average baseline 25-OH vitamin D levels were found in non-Caucasian patients (Caucasian: 27.5 ng/mL vs. non-Caucasian: 18.3 ng/mL; p<0.01) and patients with later-stage disease (Stage I: 28.8 ng/mL compared to Stage III: 21.9 ng/mL; p=0.03). Women with vitamin D deficiency were found to have lower spinal bone mineral density (<32 ng/mL: 1.09 g/cm2 compared to ≥32 ng/mL: 1.22 g/cm2; p=0.20) and hip bone mineral density (<32 ng/mL: 0.87 g/cm2 compared to ≥32 ng/mL: 0.93 g/cm2; p=0.41), however the difference was not statistically significant. High-dose vitamin D supplementation resulted in a greater increase in plasma vitamin D (+28 ng/mL; p<0.01) compared to low-dose vitamin D (+7 ng/mL; p=0.03) and no supplementation (+2 ng/mL). The authors concluded that vitamin D deficiency was extremely prevalent in women being treated for breast cancer, more prevalent in non-Caucasians, and more common in breast cancer patients who presented with later-stage breast cancer. Plasma 25-OH vitamin D levels can only be significantly increased with high-dose vitamin D supplementation; conventional low-dose vitamin D is not effective. Further research is required to investigate the association between vitamin D deficiency and bone mineral density in breast cancer patients.
Prognostic Effects of 25-Hydroxyvitamin D Levels in Early Breast Cancer Journal of Clinical Oncology, August 2009
The present prospective study was designed to investigate the association between circulating vitamin D levels and risk of progression of early breast cancer. A link between Vitamin D and breast cancer risk is biologically plausible since breast cancer cells contain vitamin D receptors which act as transcription factors to regulate gene activity. The study included a cohort of 512 women diagnosed between 1989 and 1996 with early breast cancer. Stored blood of these women was used to measure Vitamin D levels. Medical and dietary data were accessed to investigate the possible prognostic effects of vitamin D. The average age was 50.4 years, and average vitamin D was found to be 58.1 ± 23.4 nmol/L. Vitamin D levels were found to be deficient (defined as under 50 nmol/L) in 37.5% of the patients, insufficient (50 to 72 nmol/L) in 38.5%, and sufficient (more than 72 nmol/L) in 24.0%. Little variation was found in average vitamin D levels in summer versus winter months. During an average follow-up period of 11.6 years, 116 of the women had distant recurrences and 106 died. Women with deficient vitamin D levels were found to have a significantly increased risk of distant recurrence (hazard ratio (HR) = 1.94; 95% confidence interval (CI) = 1.16 - 3.25) and death (HR = 1.73; 95% CI = 1.05 - 2.86) compared with those with sufficient levels. The associations remained after individual adjustment for key tumor- and treatment-related factors. The authors conclude that vitamin D deficiency may be associated with poor outcomes in breast cancer.
Association between Plasma 25-Hydroxyvitamin D and Breast Cancer Risk Cancer Prevention Research, June 2009
The current case-control study investigated the association between breast cancer and plasma 25-hydroxyvitamin D (25-OHD) levels, a measure of body stores of vitamin D. The study included 1,026 breast cancer cases diagnosed during the period 1996 to 1997 and 1,075 population-based cancer-free controls in Long Island, New York. Face-to-face interviews were conducted and blood specimens were obtained from all of the participants. The average plasma 25-OHD concentration was found to be 27.1 (with a standard deviation of 13.0) among the breast cancer cases and 29.7 (15.1) ng/mL in the controls. Plasma 25-OHD was found to be inversely associated with risk of breast cancer in a concentration-dependent manner (Ptrend = 0.002). Compared to participants with vitamin D deficiency (defined as 25-OHD levels below 20 ng/mL), women with levels above 40 ng/mL were found to have decreased risk of breast cancer (odds ratio (OR) = 0.56; 95% confidence interval (CI) = 0.41-0.78). The vitamin-D related reduction in risk was found to be greater among postmenopausal women (OR = 0.46; 95% CI = 0.09-0.83). However, the effect of vitamin D level did not vary according to tumor hormone receptor status (e.g., estrogen receptor (ER) status). The authors conclude that whereas circulating 25-OHD levels of 32 ng/mL or higher have been found to be associated with normal bone mineral metabolism, the study data suggests that the optimal level for breast cancer prevention is 40 ng/mL.