Abstract 1870: Associations among tissue vitamin D metabolites and breast cancer risk factors in women undergoing reduction mammoplasty

Abstract

Abstract Background: Vitamin D, the precursor to the potent steroid hormone calcitriol (1,25(OH)2D), is mainly obtained through sunlight exposure, diet and supplements. Some basic science and preclinical studies indicate that vitamin D promotes differentiation and apoptosis; inhibits the proliferation and inflammation and therefore decreases the risk of developing cancer. However, most of these studies were done in cell culture and epidemiology studies utilized blood vitamin D assays. This study validates methods for measuring 25(OH)D and 1,25(OH)2D in breast tissues and investigates the relationship between tissue vitamin D, plasma vitamin D and breast cancer risk factors. Methods: To validate the assay, 44 tissue samples from 11 women with no history of breast cancer undergoing reduction mammoplasty were used to investigate the levels of vitamin D across the breast by enzyme immunoassay. Tissue and plasma 25(OH)D and 1,25(OH)2D levels were then determined in 176 subjects who have available epidemiological profiles and among whom we previously determined breast hormone and receptor levels. Correlations between tissue vitamin D metabolites with blood vitamin D metabolites, participants’ characteristics (e.g., age, race and BMI), and other hormone and receptor levels were analyzed using Pearson's correlation coefficient. Non-normally distributed continuous variables were logarithmic transformed. Partial correlation coefficients were also used to examine associations while adjusting for participant characteristics. Results: The average coefficient of variation of 25(OH)D and 1,25(OH)2D among 4 breast sections were 14.81% and 19.13%, respectively. For the entire study set, tissue 25(OH)D levels ranged between 53.24-209.36 nmol/Kg and tissue 1,25(OH)2D range was 2.48-41.91 pmol/Kg. We observed positive correlations between tissue and plasma levels of 25(OH)D (r = 0.55, p<0.0001) and 1,25(OH)2D (r = 0.58, p<0.0001). Tissue 25(OH)D and 1,25(OH)2D levels were also well correlated (r = 0.59, p<0.0001). After adjustment for BMI and age, tissue 1,25(OH)2D was positively correlated with plasma adiponectin to leptin ratio (r = 0.18, p = 0.047), and inversely correlated with tissue IGF to IGFBP3 ratio (r = -0.30, p = 0.025). None of these associations were found when comparing these factors with plasma level vitamin D metabolites. Conclusions: Our data indicate that although plasma and tissue vitamin D metabolites strongly correlate with each other, studying the target organ, namely the breast, provides greater insight into mechanistic carcinogenic relationships and how hormone levels in tissues modulate the microenvironment of the normal breast that may be related to breast cancer risk. Citation Format: Renny S. Lan, Adana A. Llanos, Theodore M. Brasky, Catalin Marian, Ramona G. Dumitrescu, Bhaskar V. S. Kallakury, Kepher H. Makambi, Jo L. Freudenheim, Peter G. Shields. Associations among tissue vitamin D metabolites and breast cancer risk factors in women undergoing reduction mammoplasty. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1870. doi:10.1158/1538-7445.AM2015-1870