Calcium plus vitamin D supplementation and the risk of breast cancer.
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.
Chlebowski
Rowan T
RT
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA. rchlebowski@gmail.com
Johnson
Karen C
KC
Kooperberg
Charles
C
Pettinger
Mary
M
Wactawski-Wende
Jean
J
Rohan
Tom
T
Rossouw
Jacques
J
Lane
Dorothy
D
O'Sullivan
Mary Jo
MJ
Yasmeen
Shagufta
S
Hiatt
Robert A
RA
Shikany
James M
JM
Vitolins
Mara
M
Khandekar
Janu
J
Hubbell
F Allan
FA
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
D017610:Calcium Compounds; D014807:Vitamin D; C104450:25-hydroxyvitamin D