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.

[{"label":"BACKGROUND","text":"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 >40 ng\/ml."},{"label":"OBJECTIVE","text":"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."},{"label":"METHODS","text":"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 <20 to \u226560 ng\/ml (<50 to \u2265150 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."},{"label":"RESULTS","text":"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 \u226560 vs <20 ng\/ml (Rate Ratio = 0.18, P = 0.006). Second, Kaplan-Meier curves for concentrations of <20, 20-39, 40-59 and \u226560 ng\/ml were significantly different (P = 0.02), with the highest proportion breast cancer-free in the \u226560 ng\/ml group (99.3%) and the lowest proportion breast cancer-free in the <20 ng\/ml group (96.8%). The proportion with breast cancer was 78% lower for \u226560 vs <20 ng\/ml (P = 0.02). Third, multivariate Cox regression revealed that women with 25(OH)D concentrations \u226560 ng\/ml had an 80% lower risk of breast cancer than women with concentrations <20 ng\/ml (HR = 0.20, P = 0.03), adjusting for age, BMI, smoking status, calcium supplement intake, and study of origin."},{"label":"CONCLUSIONS","text":"Higher 25(OH)D concentrations were associated with a dose-response decrease in breast cancer risk with concentrations \u226560 ng\/ml being most protective."}]