Abstract P3-07-01: Circulating vitamin D concentrations and breast cancer risk: A pooled analysis of 17 cohorts
Authors: Visvanathan Kala , Mondul Alison , Zeleniuch-Jacquotte Anne , Mukhtar Toqir K , Smith-Warner Stephanie A , Ziegler Regina G 
Published: May 2015

Optimizing vitamin D status through the use of supplementation and/or judicious sun exposure has been proposed as a BC risk reduction strategy. This simple and non-invasive approach to BC prevention is extremely appealing given that vitamin D concentrations in circulation are low in many individuals around the world. However, an Institute of Medicine (IOM) report found the evidence on vitamin D and breast cancer to be inconsistent. To clarify the relationship between vitamin D and breast cancer, data was pooled on approximately 25,000 women from 17 prospective cohorts worldwide. The association between pre-diagnostic circulating 25(OH)D levels, the accepted measure of vitamin D status, and breast cancer incidence was examined. For five cohorts, vitamin D status was assessed at a central laboratory (Heartland Assays, Inc.) using a direct, competitive chemiluminescence immunoassay that measures 25(OH)D2 and 25(OH)D3 equivalently. In 12 cohorts with previously measured 25(OH)D levels, a stratified sample of 29 controls was re-assayed at Heartland Assays and used to calibrate existing levels to a central assay using robust linear regression analyses. We standardized 25(OH) D levels for season using a periodic sine/cosine function. Conditional logistic regression analyses were performed in each study and were then pooled to generate pooled odds ratios by study-specific quantiles, consortium wide-quantiles, absolute cut points based on IOM guidance.

Our preliminary analyses included 10,353 cases of incident invasive breast cancer (5305 estrogen receptor (ER) positive cases and 1311 (ER) negative cases and 12,313 matched controls. Median calibrated 25(OH)D levels in controls varied from 33 to 70 nmol/L across the cohorts. The consortium-wide median 25(OH)D among controls was 22% higher in summer as compared to winter months. Across all studies, median age at blood draw was 41 to 70 years; and median elapsed time from blood draw to diagnosis ranged from 2 to 13 years. The pooled odds ratio of breast cancer, comparing the highest to lowest study-specific 25(OH)D quintile, was 0.99 (95% confidence interval 0.90-1.08) after adjusting for body mass index, physical activity, menopausal status, menopausal hormone therapy use, parity/age at first birth, and family history of breast cancer. Results were not significantly different in analyses stratified by age of diagnosis (&lt;50, 50-60, 60+ y).or by ER status. When calibrated circulating 25(OH)D levels were categorized based on the IOM definitions of "deficiency", "inadequacy", "adequacy", and "beyond adequacy", risk was similar across the categories. Further analyses are ongoing to examine especially low and high 25(OH)D concentrations, whether the vitamin D association varies according to tumor characteristics, the importance of elapsed time between blood draw and diagnosis. These will be completed before the meeting.

In conclusion, preliminary results from the largest pooled analysis of prospective studies to date show no association between 25(OH)D levels and breast cancer risk and therefore suggest that increasing Vitamin D levels may not be an effective risk reduction strategy for breast cancer.

Citation Format: Kala Visvanathan, Alison Mondul, Anne Zeleniuch-Jacquotte, Toqir K Mukhtar, Stephanie A Smith-Warner, Regina G Ziegler, On Behalf of Investigators in the Vitamin D Pooling Project of Breast and Colorectal Cancer. Circulating vitamin D concentrations and breast cancer risk: A pooled analysis of 17 cohorts [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-07-01.