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Cancer Prev Res (Phila). 2019 Jul;12(7):481-490. doi: 10.1158/1940-6207.CAPR-18-0444. Epub 2019 May 28.

Randomized Double-Blind Placebo-Controlled Biomarker Modulation Study of Vitamin D Supplementation in Premenopausal Women at High Risk for Breast Cancer (SWOG S0812).

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Columbia University Irving Medical Center, New York, New York.
Fred Hutchinson Cancer Research Center, Seattle, Washington.
Columbia University Irving Medical Center, New York, New York.
SWOG Statistics and Data Management Center, Seattle, Washington.
William Beaumont Hospital, Beaumont NCORP, Troy, Michigan.
Cancer Care Specialists of Central Illinois, Heartland NCORP, Decatur, Illinois.
University of Texas, MD Anderson Cancer Center, Houston, Texas.
Anderson Area Cancer Center, Southeast Clinical Oncology Research (SCOR) Consortium NCORP, Anderson, South Carolina.
Lahey Hospital and Medical Center, Burlington, Massachusetts.
City of Hope Medical Center, Duarte, California.
Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland.
Swedish Cancer Institute, Pacific Cancer Research Consortium NCORP, Seattle, Washington.


Observational studies have reported an inverse association between vitamin D intake and breast cancer risk. We examined whether vitamin D supplementation in high-risk premenopausal women reduces mammographic density (MD), an established breast cancer risk factor. We conducted a multicenter randomized double-blind placebo-controlled trial in premenopausal women at high risk for breast cancer [5-year risk ≥ 1.67%, lifetime risk ≥ 20%, lobular carcinoma in situ, prior stage 0-II breast cancer, hereditary breast cancer syndrome, or high MD (heterogeneously/extremely dense)], with a baseline serum 25-hydroxyvitamin D [25(OH)D] ≤ 32 ng/mL. Participants were randomized to 12 months of vitamin D3 20,000 IU/week or matching placebo. The primary endpoint was change in MD from baseline to 12 months using the Cumulus technique. Secondary endpoints included serial blood biomarkers [25(OH)D, 1,25-dihydroxyvitamin D (1,25(OH)D), insulin-like growth factor (IGF)-1, IGF-binding protein-3] and MD change at 24 months. Among 208 women randomized, median age was 44.6 years, 84% were white, 33% had baseline 25(OH)D < 20 ng/mL, and 78% had high baseline MD. Comparing the active and placebo groups at 12 months, MD changes were small and did not significantly differ. Mean MD changes at 12 and 24 months were -0.3% and -1.2%, respectively, in the active arm and +1.5% and +1.6% with placebo (P > 0.05). We observed a mean change in serum 25(OH)D of +18.9 versus +2.8 ng/mL (P < 0.01) and IGF-1 of -9.8 versus -1.8 ng/mL (P = 0.28), respectively. At 12 months, MD was positively correlated with serum IGF-1 and IGF-1/IGFBP-3 (P < 0.01). This trial does not support the use of vitamin D supplementation for breast cancer risk reduction.

[Available on 2020-07-01]

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