Vitamin D and Calcium Supplementation and One-Year Change in Mammographic Density in the Women's Health Initiative Calcium and Vitamin D Trial

Division ofBiostatistics and Epidemiology,University of Massachusetts, Amherst, Massachusetts 01003, USA.
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.13). 03/2012; 21(3):462-73. DOI: 10.1158/1055-9965.EPI-11-1009
Source: PubMed


Calcium and vitamin D may be inversely related to breast cancer risk, in part by affecting mammographic density. However, results from previous, mostly cross-sectional studies have been mixed, and there have been few randomized clinical trials of the effect of calcium and vitamin D supplementation on change in mammographic density.
We assessed the effect of one year of supplementation on mammographic density in 330 postmenopausal women enrolled in the Women's Health Initiative hormone therapy (HT) and calcium and vitamin D (CaD) trials. Women were randomized to receive 1,000 mg/d of elemental calcium carbonate plus 400 IU/d of vitamin D(3) or placebo.
After approximately one year, mammographic density decreased 2% in the CaD supplementation group and increased 1% in the placebo group (ratio of means = 0.97; 95% CI = 0.81-1.17). Results suggested potential interaction by HT use (P = 0.08). Among women randomized to HT placebo, the ratio of mean density comparing CaD supplementation and placebo groups was 0.82 (95% CI = 0.61-1.11) vs. 1.16 (95% CI = 0.92-1.45) in women randomized to active HT. In sensitivity analyses limited to women taking ≥ 80% of study supplements, ratios were 0.67 (95% CI = 0.41-1.07) in women not assigned to HT and 1.07 (95% CI = 0.79-1.47) women assigned to HT.
We observed no overall effect of vitamin D and calcium supplementation on mammographic density after one year.
Potential interaction between these nutrients and estrogen as related to mammographic density warrants further study.

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    • "However, we did observe an inverse association with dense area based upon season, which needs to be replicated in larger studies. Since a one-time measurement of serum 25(OH)D may not reflect lifetime exposure to vitamin D, future prospective studies should examine changes in vitamin D exposure over time in relation to MD and breast cancer risk, since few longitudinal studies to date have documented changes in vitamin D status with changes in MD over time [24]. "
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    ABSTRACT: Vitamin D, which influences cellular proliferation and breast tissue characteristics, has been inversely correlated with breast cancer risk. Dietary vitamin D intake has been associated with lower mammographic density (MD), a strong intermediate marker of breast cancer risk. We examined the relationship between MD and serum 25-hydroxyvitamin D [25(OH)D], an integrated measure of vitamin D status from dietary sources and sunlight exposure, in a multi-ethnic cohort of women undergoing screening mammography. We recruited women age 40-60 years without a history of breast cancer at the time of their routine screening mammogram, and conducted in-person interviews and collected blood specimens. We enrolled 195 women from 2007-2008, 120 gave blood, and 114 were evaluable, including 25% white, 41% African American, 18% African Caribbean, and 16% Hispanic. We digitized mammograms and calculated percent density, dense area, and non-dense area on cranial-caudal images. We measured serum 25(OH)D in batched, archived specimens. Median serum 25(OH)D was 22 ng/ml (range, 8-66 ng/ml). In univariable analysis, higher serum 25(OH)D was associated with white race, higher educational level, ever breast feeding, and blood draw during the summer. After adjusting for body mass index and other confounders, we found no association between serum 25(OH)D and different measures of MD. However, when stratified by season, 25(OH)D was inversely associated with dense area during July-December (p = 0.034). Overall, our findings suggest that circulating vitamin D, a potentially modifiable breast cancer risk factor, is not associated with MD; the seasonal effects we observed need to be replicated in larger cohorts.
    Nutrition & Metabolism 04/2014; 11(1):18. DOI:10.1186/1743-7075-11-18 · 3.26 Impact Factor
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    • "Similar results were found when intake from food and supplements were analyzed together. Out of the remaining seven studies, two included only postmenopausal women and neither found an association between vitamin D and calcium intake and BD [19] [20]. An additional four studies reported signi�cant associations between vitamin D and calcium overall; however, the results in postmenopausal women were considerably weaker than observed in premenopausal women [14] [26] [27]. "
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    ABSTRACT: Studies have shown inconsistent results regarding the association between dietary factors across the lifespan and breast density and breast cancer in women. Breast density is a strong risk factor for breast cancer, and the mechanism through which it influences cancer risk remains unclear. Breast density has been shown to be modifiable, potentially through dietary modifications. The goal of this paper is to summarize the current studies on diet and diet-related factors across all ages, determine which dietary factors show the strongest association with breast density, the most critical age of exposure, and identify future directions. We identified 28 studies, many of which are cross-sectional, and found that the strongest associations are among vitamin D, calcium, dietary fat, and alcohol in premenopausal women. Longitudinal studies with repeated dietary measures as well as the examination of overall diet over time are needed to confirm these findings.
    02/2013; 2013:808317. DOI:10.1155/2013/808317
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    ABSTRACT: Vitamin D deficiency and low calcium intake are considered risk factors for several cancers. Vitamin D, synthesized in the skin or ingested through the diet, is transformed through two hydroxylation steps to the active metabolite, 1α,25-dihydroxyvitamin D3 (1,25-D3). 25-hydroxylases in the liver are responsible for the first hydroxylation step. The ultimate activation is performed by the renal 25-hydroxyvitamin D 1α-hydroxylase (CYP27B1), while the 1,25-dihydroxyvitamin D-24-hydroxylase (CYP24A1) in the kidneys degrades the active metabolite. These two renal vitamin D hydroxylases control the endocrine serum 1,25-D3 levels, and are responsible for maintaining mineral homeostasis. In addition, the active vitamin D hormone 1,25-D3 regulates cellular proliferation, differentiation, and apoptosis in multiple tissues in a paracrine/autocrine manner. Interestingly, it is the low serum level of the precursor 25-hydroxyvitamin D3 (25-D3) that predisposes to numerous cancers and other chronic diseases, and not the serum concentration of the active vitamin D hormone. The extrarenal autocrine/paracrine vitamin D system is able to synthesize and degrade locally the active 1,25-D3 necessary to maintain normal cell growth and to counteract mitogenic stimuli. Thus, vitamin D hydroxylases play a prominent role in this process. The present review describes the role of the vitamin D hydroxylases in cancer pathogenesis and the cross-talk between the extra-renal autocrine/paracrine vitamin D system and calcium in cancer prevention.
    Anti-cancer agents in medicinal chemistry 10/2012; 13(1). DOI:10.2174/187152013804487434 · 2.47 Impact Factor
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