W24 - CaD Trial and Breast Cancer Serum Vitamin D Study in the WHI
This page provides study documentation for Core Study W24. For description of the specimen results, see Specimen Results Description (open to public). Data sets of the specimen results are included in the existing WHI datasets located on the WHI Data on this site (sign in and a completed Data Distribution Agreement are required; see details on the Data site).
Investigator Names and Contact Information
Core study approved by WHI Steering Committee
Introduction/Intent
Previous studies have suggested that there is a relationship between baseline levels of vitamin D and breast cancer risk. The interaction however is far from conclusive with several papers suggesting a decrease in breast cancer risk with vitamin D sufficiency. There have been no reported prospective intervention studies that have extended this potential relationship to determine if treatment with vitamin D reduces breast cancer risk.
The relationship between calcium plus vitamin D (CaD) supplementation and breast cancer risk was the aim of one priority paper from the WHI CaD trial. Data from those analyses revealed (1) a trend (p=0.053) towards an decrease in breast cancer risk with higher levels of vitamin D intake in the placebo women in the CaD trial and (2) no overall significant effect of CaD supplementation on breast cancer risk (hazard ration ; 95% confidence interval). However, when preliminary analyses examined the relationship between quartiles of vitamin D intake (determined from diet and supplement use), there was a suggestion of an increase in breast cancer risk with CaD in women with a total daily vitamin D intake < 200 international units (I.U.) and in those women with baseline vitamin D intakes that exceeded 600 I.U.
The ability of daily vitamin D exposure as assessed by medication and supplement questionnaire and food frequency is limited. The gold standard to detect and confirm vitamin D deficiency, insufficiency and sufficiency is based upon the serum 25(OH) vitamin D levels. In order to extend the observations from these preliminary data analyses and to contribute to greater elucidation of the role of vitamin D (and calcium balance) on breast cancer risk, we propose to examine 25(OH) vitamin D in breast cancer cases and controls from the WHI CaD trial. The authors of the priority manuscript on CaD and breast cancer have committed to waiting until these analytes are complete to ensure inclusion of these data into the priority paper.
We propose a case-control study to examine 25(OH) vitamin D levels in all breast cancer cases and controls from subjects who enrolled in the WHI CaD trial to examine hypotheses focused on examining (1) the association of increased breast cancer risk in women with low vitamin D stores and (2) the relationship between baseline vitamin D exposure and subsequent risk of breast cancer after CaD intervention. This study should use a case-control design as the relationship between baseline vitamin D and breast cancer risk is still controversial and additional data exploring this association will significantly contribute to the field.
Materials/Methods
For studies examining the association of vitamin D exposure and risk for breast cancer, a case-control design will be used. The more efficient case- only analysis will be used for analyses examining the interaction of baseline 25(OH) vitamin D with CaD intervention effect on risk for breast cancer.
In a case-only analysis, the power to detect an interaction between serum levels and supplements is determined by testing the distribution cases to the two experimental arms by levels of serum 25(OH) vitamin D. As a simplifying approximation, we consider the comparison of highest to lowest quartile of serum levels. For this test, the power is 86% for a relative risk of 1.7 and 64% for a relative risk of 1.5. A test for trend would provide a more powerful result. (A similar analysis using total vitamin D intake data gives an estimated relative risk of 1.7).Results/Findings
See Publications: 470, 876, 878, 910, 1121.
WHI publications by study lists published WHI papers that have been generated by ancillary studies. A complete list of WHI papers is available in the Bibliography section of this website.