Journal Article

Calcium Plus Vitamin D Supplementation and the Risk of Breast Cancer

Rowan T. Chlebowski, Karen C. Johnson, Charles Kooperberg, Mary Pettinger, Jean Wactawski-Wende, Tom Rohan, Jacques Rossouw, Dorothy Lane, Mary Jo O’Sullivan, Shagufta Yasmeen, Robert A. Hiatt, James M. Shikany, Mara Vitolins, Janu Khandekar and F. Allan Hubbell

in JNCI: Journal of the National Cancer Institute

Volume 100, issue 22, pages 1581-1591
Published in print November 2008 | ISSN: 0027-8874
Published online November 2008 | e-ISSN: 1460-2105 | DOI:
Calcium Plus Vitamin D Supplementation and the Risk of Breast Cancer

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Although some observational studies have associated higher calcium intake and especially higher vitamin D intake and 25-hydroxyvitamin D levels with lower breast cancer risk, no randomized trial has evaluated these relationships.


Postmenopausal women (N = 36 282) who were enrolled in a Women's Health Initiative clinical trial were randomly assigned to 1000 mg of elemental calcium with 400 IU of vitamin D3 daily or placebo for a mean of 7.0 years to determine the effects of supplement use on incidence of hip fracture. Mammograms and breast exams were serially conducted. Invasive breast cancer was a secondary outcome. Baseline serum 25-hydroxyvitamin D levels were assessed in a nested case–control study of 1067 case patients and 1067 control subjects. A Cox proportional hazards model was used to estimate the risk of breast cancer associated with random assignment to calcium with vitamin D3. Associations between 25-hydroxyvitamin D serum levels and total vitamin D intake, body mass index (BMI), recreational physical activity, and breast cancer risks were evaluated using logistic regression models. Statistical tests were two-sided.


Invasive breast cancer incidence was similar in the two groups (528 supplement vs 546 placebo; hazard ratio = 0.96; 95% confidence interval = 0.85 to 1.09). In the nested case–control study, no effect of supplement group assignment on breast cancer risk was seen. Baseline 25-hydroxyvitamin D levels were modestly correlated with total vitamin D intake (diet and supplements) (r = 0.19, P < .001) and were higher among women with lower BMI and higher recreational physical activity (both P < .001). Baseline 25-hydroxyvitamin D levels were not associated with breast cancer risk in analyses that were adjusted for BMI and physical activity (Ptrend = .20).


Calcium and vitamin D supplementation did not reduce invasive breast cancer incidence in postmenopausal women. In addition, 25-hydroxyvitamin D levels were not associated with subsequent breast cancer risk. These findings do not support a relationship between total vitamin D intake and 25-hydroxyvitamin D levels with breast cancer risk.

Journal Article.  5695 words.  Illustrated.

Subjects: Medical Oncology

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