Chlebowski Rowan T, Johnson Karen C, Kooperberg Charles, Pettinger Mary, Wactawski-Wende Jean, Rohan Tom, Rossouw Jacques, Lane Dorothy, O'Sullivan Mary Jo, Yasmeen Shagufta, Hiatt Robert A, Shikany James M, Vitolins Mara, Khandekar Janu, Hubbell F Allan
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
J Natl Cancer Inst. 2008 Nov 19;100(22):1581-91. doi: 10.1093/jnci/djn360. Epub 2008 Nov 11.
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.
尽管一些观察性研究表明，较高的钙摄入量，尤其是较高的维生素D摄入量和25-羟维生素D水平与较低的乳腺癌风险相关，但尚无随机试验评估过这些关系。
参加妇女健康倡议临床试验的绝经后妇女（N = 36282）被随机分配，每天服用1000毫克元素钙加400国际单位维生素D3或安慰剂，平均服用7.0年，以确定补充剂使用对髋部骨折发生率的影响。定期进行乳房X光检查和乳房检查。浸润性乳腺癌是次要结果。在一项对1067例病例患者和1067例对照受试者的巢式病例对照研究中评估了基线血清25-羟维生素D水平。使用Cox比例风险模型估计随机分配到钙加维生素D3与乳腺癌相关的风险。使用逻辑回归模型评估25-羟维生素D血清水平与总维生素D摄入量、体重指数（BMI）、休闲体育活动和乳腺癌风险之间的关联。统计检验为双侧检验。
两组的浸润性乳腺癌发病率相似（补充剂组528例，安慰剂组546例；风险比 = 0.96；95%置信区间 = 0.85至1.09）。在巢式病例对照研究中，未观察到补充剂组分配对乳腺癌风险有影响。基线25-羟维生素D水平与总维生素D摄入量（饮食和补充剂）适度相关（r = 0.19，P <.001），在BMI较低和休闲体育活动较多的女性中更高（均P <.001）。在根据BMI和体育活动进行调整的分析中，基线25-羟维生素D水平与乳腺癌风险无关（P趋势 = 0.20）。
补充钙和维生素D并未降低绝经后妇女浸润性乳腺癌的发病率。此外，25-羟维生素D水平与随后的乳腺癌风险无关。这些发现不支持总维生素D摄入量和25-羟维生素D水平与乳腺癌风险之间存在关联。
