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, F. Allan Hubbell

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Abstract

Background: 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. Methods: 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 D 3. 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. Results: 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). Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)1581-1591
Number of pages11
JournalJournal of the National Cancer Institute
Volume100
Issue number22
DOIs
StatePublished - Nov 1 2008

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Chlebowski, R. T., Johnson, K. C., Kooperberg, C., Pettinger, M., Wactawski-Wende, J., Rohan, T., Rossouw, J., Lane, D., O'Sullivan, M. J., Yasmeen, S., Hiatt, R. A., Shikany, J. M., Vitolins, M., Khandekar, J., & Hubbell, F. A. (2008). Calcium plus vitamin D supplementation and the risk of breast cancer. Journal of the National Cancer Institute, 100(22), 1581-1591. https://doi.org/10.1093/jnci/djn360