36,282 postmenopausal women were enrolled in a Women’s Health Initiative clinical trial to determine the effects of calcium and vitamin D on the incidence of hip fracture. Invasive breast cancer was a secondary outcome measure. Patients were randomly assigned to 1000 mg of calcium with 400 IU of vitamin D3 daily, or placebo for an average of 7.0 years. Mammograms, breast exams, serum 25-hydroxyvitamin D levels were assessed in a nested case-control study of 1067 breast cancer cases and 1067 controls. The risk of breast cancer associated with random assignment to calcium with vitamin D3 was estimated using a mathematical model. The incidence of invasive breast cancer was similar in the calcium with vitamin D group compared to the placebo group, and baseline 25-hydroxyvitamin D levels were not associated with breast cancer risk after adjusting for body mass index and physical activity. These results do not support a relationship between total vitamin D supplemental intake and 25-hydroxyvitamin D levels with breast cancer risk.
Commentary
This randomized, double-blind, placebo-controlled trial of daily supplementation of 1000 mg of elemental calcium with 400 IU vitamin D3 had no effect on the incidence of breast cancer. Some observational studies have demonstrated an association between higher calcium and vitamin D intake and reductions in breast cancer risk in postmenopausal women, while others have not. Studies in postmenopausal women have also been mixed in showing an association with lowered breast cancer risk in those with higher serum levels of 25-hydroxyvitamin D. Several thoughts regarding these mixed results are worth considering: 1) Different thresholds of serum 25-hydroxyvitamin D are used to assess associations and it may be that a higher threshold (52 nmol/L says some research; 75 nmol/L says other research) is needed to show an association. 2) Higher doses of vitamin D may be needed to demonstrate consistent results. 3) The doses of vitamin D used in different trials are not consistent. 4) The seven year duration of the current study may be insufficient given the latency of breast cancer. 5) Results may be confounded by lean women vs. overweight or obese women, recreational activity and sunlight exposure.
Given the wide variety of preventive effects of vitamin D supplementation, the multiple disease reduction benefits associated with higher serum levels, and the selected benefits on intervention with supplementation, for now, I will continue to be assertive in vitamin D dosing. The list of benefits and potential benefits spans so many diseases (heart disease, hypertension, peripheral vascular disease, osteoarthritis, osteoporosis, fractures, autoimmune diseases, depression, insulin resistance, ovarian cancer, breast cancer, colon cancer), that it remains compelling to recommend one of the most economical and safe supplements currently available.
References
- Chlebowski R, Johnson K, Kooperberg C, et al. Calcium plus vitamin D supplementation and the risk of breast cancer. J Natl Cancer Inst 2008 100: 1561.
