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J Natl Cancer Inst. 2008 Nov 19;100(22):1581-91. doi: 10.1093/jnci/djn360. Epub 2008 Nov 11.

Calcium plus vitamin D supplementation and the risk of breast cancer.

Collaborators (220)

Nabel E, Rossouw J, Ludlam S, McGowan J, Geller N, Ford L, Prentice R, Anderson G, LaCroix A, Patterson R, McTiernan A, Cochrane B, Hunt J, Tinker L, Kooperberg C, McIntosh M, Wang CY, Chen C, Bowen D, Kristal A, Stanford J, Urban N, Weiss N, White E, Stein E, Laskarzewski P, Cummings SR, Nevitt M, Palermo L, Harnack L, Cammarata F, Lindenfelser S, Psaty B, Heckbert S, Wassertheil-Smoller S, Frishman W, Wylie-Rosett J, Barad D, Freeman R, Rajkovic A, Hays J, Young R, Sangi-Haghpeykar H, Manson JE, Rexrode KM, Walsh B, Gaziano JM, Bueche M, Eaton CB, Cyr M, Sloane G, Phillips L, Butler V, Porter V, Beresford SA, Taylor VM, Woods NF, Henderson M, Andersen R, Martin L, Hsia J, Gaba N, Katz R, Chlebowski R, Detrano R, Nelson A, Geller M, Michael Y, Whitlock E, Stevens V, Karanja N, Caan B, Sidney S, Hirata GB, Kotchen JM, Barnabei V, Kotchen TA, Gilligan MA, Neuner J, Howard BV, Adams-Campbell L, Lessin L, Iglesia C, Mickel LK, Van Horn L, Greenland P, Khandekar J, Liu K, Rosenberg C, Black H, Powell L, Mason E, Gulati M, Stefanick ML, Hlatky MA, Chen B, Stafford RS, Mackey S, Lane D, Granek I, Lawson W, Messina C, San Roman G, Jackson R, Harris R, Paskett E, Mysiw WJ, Blumenfeld M, Lewis CE, Oberman A, Shikany JM, Safford M, Thomson CA, Bassford T, Ritenbaugh C, Chen Z, Ko M, Wactawski-Wende J, Trevisan M, Smit E, Graham S, Chang J, Robbins J, Yasmeen S, Hubbell FA, Frank G, Wong N, Greep N, Monk B, Nathan L, Heber D, Elashoff R, Liu S, Langer RD, Criqui MH, Talavera GT, Garland CF, Allison MA, Gass M, Watts N, Limacher M, Perri M, Kaunitz A, Stan Williams R, Brinson Y, Curb JD, Petrovitch H, Rodriguez B, Masaki K, Blanchette P, Wallace R, Torner J, Johnson S, Snetselaar L, Robinson J, Ockene J, Rosal M, Ockene I, Yood R, Aronson P, Lasser N, Singh B, Lasser V, Kostis J, McGovern P, O'Sullivan MJ, Parker L, Potter J, Fernandez D, Caralis P, Margolis KL, Grimm RH, Perron MF, Bjerk C, Kempainen S, Brunner R, Graettinger W, Oujevolk V, Bloch M, Heiss G, Haines P, Ontjes D, Sueta C, Wells E, Kuller L, Cauley J, Milas NC, Johnson K, Satterfield S, Li R, Connelly S, Tylavsky F, Brzyski R, Schenken R, Sarto GE, Laube D, McBride P, Mares J, Loevinger B, Vitolins M, Burke G, Crouse R, Washburn S, Shumaker S, Rapp S, Legault C, Espeland M, Coker L, Hays J, Foreyt J, Assaf AR, Hall D, Miller V, Valanis B, Hiatt R, Pottern L, Meyskens F Jr, Judd H, Liu J, Watts N.

Author information

  • 1Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA. rchlebowski@gmail.com



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 D(3) 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.


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 (P(trend) = .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.

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