Vitamin D and mammographic density in postmenopausal women: A cohort study nested within a chemoprevention trial
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Background: Vitamin D may be important in the causal pathway to breast cancer (BC) by influencing mammographic breast density (MD). However, previous study results in postmenopausal women are inconsistent. Study objectives were to prospectively examine the relationship between biomarkers of vitamin D (25-OH-D) and percent MD in postmenopausal women at northern latitudes. Potential effect modification by exemestane therapy, calcium or genetic polymorphisms in the vitamin D pathway was also examined. Methods: This study evaluated a sub-cohort of postmenopausal women at elevated BC risk who participated in the NCIC Clinical Trials Group placebo-controlled MAP.3 trial with exemestane. Levels of 25-OH-D were measured using LC-MS/MS from serum samples collected at baseline and year 1, averaged and adjusted for month of collection. Baseline and follow-up (≥ 3 year) percent MD was centrally assessed from film and digital mammograms with Cumulus software. Multivariable linear regression was used to estimate the effect of 25-OH-D on log transformed percent MD at follow-up and on the change in percent MD from baseline. Percent MD was also dichotomized and multivariable logistic regression was used to evaluate 25-OH-D levels between 1) women with lower (<25%) compared with higher (≥25%) percent MD and 2) women with a decrease compared with no change or an increase in percent MD over time. Results: Percent MD was measured for 568 participants with a follow-up mammogram and for 388 participants with a baseline mammogram in the same format as the follow-up. The geometric mean percent MD of the follow-up mammograms was 4.3% and few women (13.4%) had percent MD ≥ 25%. The unadjusted mean 25-OH-D concentration was 36.5 ng/mL (SD=10.6) based on pooled baseline and year one samples. After controlling for age, month of sampling and potential confounders, 25-OH-D was not predictive of log transformed percent MD at follow-up (p=0.36) or with annual mean changes from baseline (p=0.33). Similarly, results from the logistic regression analyses were not statistically significant and no interactions with exemestane, calcium or genetic polymorphisms were detected. Conclusion: No association was observed between vitamin D levels and percent MD at ≥3 year follow-up or change in percent MD from baseline.