title: Calcium plus vitamin D supplementation and the risk of breast cancer.
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 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.
  
  
  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 (P(trend) = .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.
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA. rchlebowski@gmail.com
authors.forename: Rowan T
authors.initials: RT
authors.lastname: Chlebowski
authors.forename: Karen C
authors.initials: KC
authors.lastname: Johnson
authors.forename: Charles
authors.initials: C
authors.lastname: Kooperberg
authors.forename: Mary
authors.initials: M
authors.lastname: Pettinger
authors.forename: Jean
authors.initials: J
authors.lastname: Wactawski-Wende
authors.forename: Tom
authors.initials: T
authors.lastname: Rohan
authors.forename: Jacques
authors.initials: J
authors.lastname: Rossouw
authors.forename: Dorothy
authors.initials: D
authors.lastname: Lane
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: O'Sullivan
authors.forename: Shagufta
authors.initials: S
authors.lastname: Yasmeen
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hiatt
authors.forename: James M
authors.initials: JM
authors.lastname: Shikany
authors.forename: Mara
authors.initials: M
authors.lastname: Vitolins
authors.forename: Janu
authors.initials: J
authors.lastname: Khandekar
authors.forename: F Allan
authors.initials: FA
authors.lastname: Hubbell
mesh_terms: D000368:Aged; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000517:prevention & control; D017610:Calcium Compounds / Q000008:administration & dosage*; D018270:Carcinoma, Ductal, Breast / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000517:prevention & control; D016022:Case-Control Studies; D019587:Dietary Supplements; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008327:Mammography; D008875:Middle Aged; D016017:Odds Ratio; D018579:Patient Selection; D017698:Postmenopause; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D014807:Vitamin D / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D017610:Calcium Compounds; D014807:Vitamin D; C104450:25-hydroxyvitamin D