A randomized controlled trial of calcium plus vitamin D supplementation and risk of benign proliferative breast disease

Abstract

Experimental evidence provides strong support for anti-carcinogenic effects of calcium and vitamin D with respect to breast cancer. Observational epidemiologic data also provide some support for inverse associations with risk. We tested the effect of calcium plus vitamin D supplementation on risk of benign proliferative breast disease, a condition which is associated with increased risk of breast cancer. We used the Women’s Health Initiative randomized controlled trial. The 36,282 participants were randomized either to 500 mg of elemental calcium as calcium carbonate plus 200 IU of vitamin D3 (GlaxoSmithKline) twice daily (n = 18,176) or to placebo (n = 18,106). Regular mammograms and clinical breast exams were performed. We identified women who had had a biopsy for benign breast disease and subjected histologic sections from the biopsies to standardized review. After an average follow-up period of 6.8 years, 915 incident cases of benign proliferative breast disease had been ascertained, with 450 in the intervention group and 465 in the placebo group. Calcium plus vitamin D supplementation was not associated with altered risk of benign proliferative breast disease overall (hazard ratio = 0.99, 95% confidence interval = 0.86–1.13), or by histologic subtype. Risk varied significantly by levels of age at baseline, but not by levels of other variables. Daily use of 1,000 mg of elemental calcium as calcium carbonate plus 400 IU of vitamin D3 for almost 7 years by postmenopausal women did not alter the overall risk of benign proliferative breast disease.

Obesity and increased risk of cancer: Does decrease of serum 25‐hydroxyvitamin D level with increasing body mass index explain some of the association?

“…Other clinical trials have failed to reveal any correlation between vitamin D intake and cancer risk or invasiveness [49,50]. The dose of 400 IU/day of vitamin D supplementation used in these studies appeared to be inadequate for cancer prevention, and, according to Gorham et al, should be increased up to 2000 IU/day [6].…”

Levels of Serum 25-Hydroxy-Vitamin D in Benign and Malignant Breast Masses

“…placebo in normal women showed no difference between the two groups in development of proliferative benign breast disorders after seven years (Rohan et al, 2009). Nevertheless, some abnormalities were noticed by Lopes et al in the expression of vitamin D receptors in some benign breast diseases (Lopes et al, 2012).…”

Calcium Plus Vitamin D Supplementation and Health Outcomes Five Years After Active Intervention Ended: The Women's Health Initiative

“…Additionally, in the current study, supplementation had no influence on benign proliferative breast disease. 33 As a result, the lower in situ breast cancer incidence in the supplement group could represent a chance finding. However, emergence of lower in situ breast cancer incidence only occurred after a long period of supplement exposure and postexposure follow-up suggests a duration effect with perhaps an influence on subsequent invasive breast cancer to emerge after still longer follow-up.…”