Vitamin D and calcium supplementation and one-year change in mammographic density in the women's health initiative calcium and vitamin D trial

Elizabeth R Bertone-Johnson, Anne McTiernan, Cynthia A Thomson, Jean Wactawski-Wende, Aaron K Aragaki, Thomas E Rohan, Mara Z Vitolins, Rulla M Tamimi, Karen C Johnson, Dorothy Lane, Kathryn M Rexrode, Jennifer D Peck, Rowan T Chlebowski, Gloria Sarto, Joann E Manson
Cancer Epidemiology, Biomarkers & Prevention 2012, 21 (3): 462-73

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: We observed no overall effect of vitamin D and calcium supplementation on mammographic density after one year.

IMPACT: Potential interaction between these nutrients and estrogen as related to mammographic density warrants further study.

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