The Influence of Vitamin D on Mammographic Density: Results from CALGB 70806 (Alliance) a Randomized Clinical Trial.

Current therapies for breast cancer prevention only prevent estrogen receptor positive (ER+) disease and toxicity limits use of these agents. Vitamin D is a potential prevention therapy for both ER+ and ER- disease and is safe with few side effects. This study evaluates the effect of 1-year of vitamin D supplementation on mammographic density (MD), a biomarker of breast cancer risk in a multicenter randomized controlled trial. Premenopausal women with ≥25% MD and no history of cancer were randomly assigned to 2,000 international units (IU) of vitamin D or placebo orally daily for 1 year. Change in percent MD was evaluated using Cumulus software after all participants completed treatment. Three hundred women enrolled between January 2011 and December 2013 with a mean age of 43 and diverse ethnicity [14% Hispanic, 12% African American (AA)]. Supplementation significantly increased vitamin D levels compared with placebo (14.5 ng/mL vs. -1.6 ng/mL; P < 0.0001) with all participants on the vitamin D arm achieving vitamin D sufficiency at 12 months. Vitamin D was safe and well tolerated. After adjustment for baseline MD, the mean between-arm difference (vitamin D vs. placebo) at 1 year was -0.75 (-0.26, 1.76; P = 0.56). A greater effect was seen for women with ≥50% MD and AA women, although neither reached significance. This randomized controlled trial demonstrated significant improvement in vitamin D levels with 2,000 IU for 1 year, with 100% of supplemented women achieving sufficiency. However, a null effect was seen regarding change in MD for premenopausal women (the primary outcome of the study). PREVENTION RELEVANCE: Current therapies for breast cancer prevention only prevent estrogen receptor positive (ER+) disease and are underutilized due to toxicity and side effects. Vitamin D is a potential prevention therapy for both ER+ and ER- disease and is safe with few side effects.

Effect of Vitamin D Supplementation on Breast Cancer Biomarkers: CALGB 70806 (Alliance) Study Design and Baseline Data.

One in eight women will develop breast cancer over their lifetime with 230,000 women diagnosed in 2015. For this reason, breast cancer prevention efforts are essential. Vitamin D, with anticancer properties, may have a role in prevention of some cancers, including breast cancer. This report discusses the rationale, study protocol, and baseline data for a clinical trial of vitamin D and its effects on breast cancer biomarkers. This study was a randomized controlled trial designed to evaluate the effect of a fixed dose of vitamin D on specfic breast cancer biomarkers. Study participants were randomized to take either vitamin D or placebo for a period of 1 year. All participants had mammograms and blood drawn for serum biomarkers. A subset of participants underwent random periareolar fine needle aspiration to draw tissue for biomarkers. From January 2011 to December 2013, 300 premenopausal women, aged 59 or younger, were recruited from 41 institutions across the United States. A total of 102 women underwent random periareolar fine needle aspiration. The last subject completed the trial in January 2015. Baseline vitamin D levels for all participants ranged from 4-72 ng/mL, with 62% of participants being vitamin D deficient at enrollment (≥30 ng/mL or ≥75 nmo-l/L). The mean body mass index was 27.0 kg/m2 (range 15.1-53.6 kg/m2). 14% and 11.7% of participants were Hispanic or African American, respectively. Accrual and enrollment of participants is feasible for this type of multi-center prevention trial, and it can readily be carried out in a cooperative group setting.