Breast Cancer Risk Markedly Lower With Serum 25-Hydroxyvitamin D Concentrations ≥60 Vs <20 Ng/Ml (150 Vs 50 Nmol/L): Pooled Analysis Of Two Randomized Trials And A Prospective Cohort

Background: While numerous epidemiologic studies have found an association between higher serum 25-hydroxyvitamin D [25(OH)D] concentrations and lower breast cancer risk, few have assessed this association for concentrations &gt;40 ng/ml. Objective: To investigate the relationship between 25(OH)D concentration and breast cancer risk across a broad range of 25(OH)D concentrations among women aged 55 years and older. Methods: Analyses used pooled data from two randomized clinical trials (N=1129, N=2196) and a prospective cohort (N=1713) to examine a broad range of 25(OH)D concentrations. The outcome was diagnosis of breast cancer during the observation periods (median: 4.0 years). Three analyses were conducted: 1) Incidence rates were compared according to 25(OH)D concentration from &lt;20 to ≥60 ng/ml (&lt;50 to ≥150 nmol/L), 2) Kaplan-Meier plots were developed and 3) multivariate Cox regression was used to examine the association between 25(OH)D and breast cancer risk using multiple 25(OH)D measurements. Results: Within the pooled cohort (N=5038), 77 women were diagnosed with breast cancer (age-adjusted incidence: 512 cases per 100,000 person-years). Results were similar for the three analyses. First, comparing incidence rates, there was an 82% lower incidence rate of breast cancer for women with 25(OH)D concentrations ≥60 vs &lt;20 ng/ml (Rate Ratio=0.18, <em>P</em>=0.006). Second, Kaplan-Meier curves for concentrations of &lt;20, 20-39, 40-59 and ≥60 ng/ml were significantly different (<em>P</em>=0.02), with the highest proportion breast cancer-free in the ≥60 ng/ml group (99.3%) and the lowest proportion breast cancer-free in the &lt;20 ng/ml group (96.8%). The proportion with breast cancer was 78% lower for ≥60 vs &lt;20 ng/ml (<em>P</em>=0.02). Third, multivariate Cox regression revealed that women with 25(OH)D concentrations ≥60 ng/ml had an 80% lower risk of breast cancer than women with concentrations &lt;20 ng/ml (HR=0.20, <em>P</em>=0.03), adjusting for age, BMI, smoking status, calcium supplement intake, and study of origin. Conclusions: Higher 25(OH)D concentrations were associated with a dose-response decrease in breast cancer risk with concentrations ≥60 ng/ml being most protective.