title: The effect of calcium plus vitamin D on risk for invasive cancer: results of the Women's Health Initiative (WHI) calcium plus vitamin D randomized clinical trial.
abstract: In the Women's Health Initiative (WHI) trial of calcium plus vitamin D (CaD), we examined the treatment effect on incidence and mortality for all invasive cancers. Postmenopausal women (N = 36,282) were randomized to 1,000 mg of elemental calcium with 400 IU vitamin D3 or placebo. Cox models estimated risk of cancer incidence and mortality. After 7.0 yr, 1,306 invasive cancers were diagnosed in the supplement and 1,333 in the placebo group [hazard ratio (HR) = 0.98; CI = 0.90, 1.05, unweighted P = 0.54]. Mortality did not differ between supplement (315, annualized% = .26) and placebo [(347, 0.28%; P = 0.17; HR = 0.90 (0.77, 1.05)]. Significant treatment interactions on incident cancer were found for family history of cancer, personal total intake of vitamin D, smoking, and WHI dietary trial randomized group. Calcium/vitamin D supplementation did not reduce invasive cancer incidence or mortality. Supplementation lowered cancer risk in the WHI healthy diet trial arm and in women without a first-degree relative with cancer. The interactions are only suggestive given multiple testing considerations. The low vitamin D dose provided, limited adherence, and lack of serum 25(OH)D values should be considered when interpreting these findings.
authors.affiliation: Department of Family and Community Medicine, University of Nevada School of Medicine, Reno, Nevada 89557, USA. bbrunner@medicine.nevada.edu
authors.forename: Robert L
authors.initials: RL
authors.lastname: Brunner
authors.forename: Jean
authors.initials: J
authors.lastname: Wactawski-Wende
authors.forename: Bette J
authors.initials: BJ
authors.lastname: Caan
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Cochrane
authors.forename: Rowan T
authors.initials: RT
authors.lastname: Chlebowski
authors.forename: Margery L S
authors.initials: ML
authors.lastname: Gass
authors.forename: Elizabeth T
authors.initials: ET
authors.lastname: Jacobs
authors.forename: Andrea Z
authors.initials: AZ
authors.lastname: LaCroix
authors.forename: Dorothy
authors.initials: D
authors.lastname: Lane
authors.forename: Joseph
authors.initials: J
authors.lastname: Larson
authors.forename: Karen L
authors.initials: KL
authors.lastname: Margolis
authors.forename: Amy E
authors.initials: AE
authors.lastname: Millen
authors.forename: Gloria E
authors.initials: GE
authors.lastname: Sarto
authors.forename: Mara Z
authors.initials: MZ
authors.lastname: Vitolins
authors.forename: Robert B
authors.initials: RB
authors.lastname: Wallace
mesh_terms: D000368:Aged; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D002136:Calcium, Dietary / Q000008:administration & dosage*; D002762:Cholecalciferol / Q000008:administration & dosage*; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009026:Mortality; D009369:Neoplasms / Q000453:epidemiology*; D010349:Patient Compliance; D017698:Postmenopause; D016016:Proportional Hazards Models; D016387:Women's Health
chemical_list: D050071:Bone Density Conservation Agents; D002136:Calcium, Dietary; D002762:Cholecalciferol