Plain language summary
Numerous studies have shown an association between Vitamin D status and risk of breast cancer. However to date, there are few studies that look at concentrations of Vitamin D in excess of 100 nmol/l and breast cancer risk. This study pooled the results of 2 randomised controlled trials and one prospective cohort study to investigate the relationship between Vitamin D levels and breast cancer incidence. The pooled results included 5,038 women. The analysis revealed that women with Vitamin D status of >150 nmol/l had an 80% lower risk of breast cancer than women with Vitamin D concentrations of <50 nmol/l, adjusting for age, BMI, smoking status and calcium supplementation. The findings also show that the risk of breast cancer is dose responsive, with the lowest risk of breast cancer at Vitamin D levels of >150 nmol/l. Testing for Vitamin D status and optimising levels to >150 nmol/l could be considered as part of a strategy for breast cancer prevention.
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 >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 <20 to ≥60 ng/ml (<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 <20 ng/ml (Rate Ratio = 0.18, P = 0.006). Second, Kaplan-Meier curves for concentrations of <20, 20-39, 40-59 and ≥60 ng/ml were significantly different (P = 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 <20 ng/ml group (96.8%). The proportion with breast cancer was 78% lower for ≥60 vs <20 ng/ml (P = 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 <20 ng/ml (HR = 0.20, P = 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.