Association of baseline plasma levels of 25OH vitamin D and breast cancer risk in a chemoprevention trial.

1546 Background: Observational studies have shown a correlation of higher serum 25-hydroxyvitamin D (25OHD) concentrations and reduced cancer risk, including breast cancer (BC). We assessed the association of 25OHD and Vitamin D Receptor (VDR) polymorphisms (SNPs) with breast cancer events within a chemoprevention trial in premenopausal women at risk for BC. Methods: Premenopausal women with history of intraepithelial neoplasia (IEN) or at risk women according to the Gail model were included in a 4 arm phase II prevention trial (low dose tamoxifen vs fenrerinide vs their combination vs placebo). Level of 25OHD were measured at baseline. VDR SNPs ( FokI, BsmI, TaqI, ApaI, and Cdx2) were determined using the Applied Biosystems’ Taqman Allelic Discrimination Assay according to manufacturer’s instructions. Survival analysis for breast cancer events was performed using competing risk models, adjusted for BMI, age, season and risk strata. Results: Plasma samples were available for 228 subjects. At baseline the median plasma 25OHD concentrations were slightly higher in 53 unaffected women, 19.6 ng/ml (IQR 12.7-27.3 ng/mL) than in 175 women with IEN, 18.8 ng/ml (11.7-25.8). After a median follow up of 15 years, 79 women developed a breast cancer event, 12 had different neoplastic events. The median level of 25OHD was 19.7 ng/ml (IQR 12.8-26.1) in subjects free from oncological events and 17.8 ng/ml (9.7-23.9) in subjects with breast events. Women in the lowest 25OHD quartile (≤12 ng/ml) had an increased risk of breast cancer events: HR = 1.79 (95%CI, 1.07-2.99, p = 0.03). Considering all cancer events, the associations with 25OHD were confirmed (P = 0.005). Among the VDR SNPs the ApaI variant in homozygote or heterozygote versus wild type showed an HR of 1.83 (95%CI, 1.04-3.21 p = 0.03). Conclusions: Our results support a role of plasma vitamin D levels in breast cancer risk. Subjects in the lowest quartile had a two-fold increased risk of a cancer event. Our findings support trials of 25OHD supplementation to prevent breast cancer in 25OHD insufficient subjects.