Breast Cancer Research and Treatment

, Volume 116, Issue 2, pp 339–350 | Cite as

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

  • Thomas E. Rohan
  • Abdissa Negassa
  • Rowan T. Chlebowski
  • Clementina D. Ceria-Ulep
  • Barbara B. Cochrane
  • Dorothy S. Lane
  • Mindy Ginsberg
  • Sylvia Wassertheil-Smoller
  • David L. Page
Clinical Trial


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.


Calcium Vitamin D Benign proliferative breast disease 



The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the view of the National Institutes of Health. The authors thank the WHI investigators and staff, and the WHI participants, for their outstanding dedication and commitment.


The WHI program is funded by the National Heart, Lung and Blood Institute, U.S. Department of Health and Human Services. The present study was supported by National Cancer Institute RO1 CA 077290-07.


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Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Thomas E. Rohan
    • 1
  • Abdissa Negassa
    • 1
  • Rowan T. Chlebowski
    • 2
  • Clementina D. Ceria-Ulep
    • 3
  • Barbara B. Cochrane
    • 4
  • Dorothy S. Lane
    • 5
  • Mindy Ginsberg
    • 1
  • Sylvia Wassertheil-Smoller
    • 1
  • David L. Page
    • 6
  1. 1.Department of Epidemiology and Population HealthAlbert Einstein College of MedicineBronxUSA
  2. 2.Harbor-UCLA Medical CenterTorranceUSA
  3. 3.School of Nursing and Dental HygieneUniversity of HawaiiHonoluluUSA
  4. 4.School of NursingUniversity of WashingtonSeattleUSA
  5. 5.Department of Preventive Medicine, School of MedicineSUNY at Stony BrookStony BrookUSA
  6. 6.Vanderbilt University Medical SchoolNashvilleUSA

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