Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
PLoS One. 2011 Feb 28;6(2):e17251. doi: 10.1371/journal.pone.0017251.
Results from epidemiologic studies on the relationship between vitamin D and breast cancer risk are inconclusive. It is possible that vitamin D may be effective in reducing risk only of specific subtypes due to disease heterogeneity.
In case-control and case-series analyses, we examined serum concentrations of 25-hydroxyvitamin D (25OHD) in relation to breast cancer prognostic characteristics, including histologic grade, estrogen receptor (ER), and molecular subtypes defined by ER, progesterone receptor (PR) and HER2, among 579 women with incident breast cancer and 574 controls matched on age and time of blood draw enrolled in the Roswell Park Cancer Institute from 2003 to 2008. We found that breast cancer cases had significantly lower 25OHD concentrations than controls (adjusted mean, 22.8 versus 26.2 ng/mL, p<0.001). Among premenopausal women, 25OHD concentrations were lower in those with high- versus low-grade tumors, and ER negative versus ER positive tumors (p≤0.03). Levels were lowest among women with triple-negative cancer (17.5 ng/mL), significantly different from those with luminal A cancer (24.5 ng/mL, p = 0.002). In case-control analyses, premenopausal women with 25OHD concentrations above the median had significantly lower odds of having triple-negative cancer (OR = 0.21, 95% CI = 0.08-0.53) than those with levels below the median; and every 10 ng/mL increase in serum 25OHD concentrations was associated with a 64% lower odds of having triple-negative cancer (OR = 0.36, 95% CI = 0.22-0.56). The differential associations by tumor subtypes among premenopausal women were confirmed in case-series analyses.
In our analyses, higher serum levels of 25OHD were associated with reduced risk of breast cancer, with associations strongest for high grade, ER negative or triple negative cancers in premenopausal women. With further confirmation in large prospective studies, these findings could warrant vitamin D supplementation for reducing breast cancer risk, particularly those with poor prognostic characteristics among premenopausal women.
关于维生素 D 与乳腺癌风险之间关系的流行病学研究结果尚无定论。由于疾病异质性，维生素 D 可能仅对特定亚型的风险有效。
在病例对照和病例系列分析中，我们检查了 579 名乳腺癌患者和 574 名年龄和采血时间相匹配的对照者的血清 25-羟维生素 D（25OHD）浓度与乳腺癌预后特征之间的关系，这些特征包括组织学分级、雌激素受体（ER）以及 ER、孕激素受体（PR）和 HER2 定义的分子亚型。这些患者均于 2003 年至 2008 年期间在罗切斯特大学癌症研究所入组。我们发现，乳腺癌患者的 25OHD 浓度明显低于对照组（调整均值，22.8 与 26.2ng/mL，p<0.001）。在绝经前妇女中，25OHD 浓度在高分级与低分级肿瘤之间、ER 阴性与 ER 阳性肿瘤之间存在差异（p≤0.03）。三阴性乳腺癌患者的水平最低（17.5ng/mL），与 luminal A 型癌症（24.5ng/mL，p=0.002）显著不同。在病例对照分析中，25OHD 浓度高于中位数的绝经前妇女发生三阴性乳腺癌的几率显著低于浓度低于中位数的妇女（OR=0.21，95%CI=0.08-0.53）；血清 25OHD 浓度每增加 10ng/mL，发生三阴性乳腺癌的几率降低 64%（OR=0.36，95%CI=0.22-0.56）。在绝经前妇女中，肿瘤亚型的差异相关性在病例系列分析中得到了证实。
在我们的分析中，较高的血清 25OHD 水平与乳腺癌风险降低相关，在绝经前妇女中，与高级别、ER 阴性或三阴性癌症的相关性最强。在大型前瞻性研究中进一步证实后，这些发现可能支持维生素 D 补充以降低乳腺癌风险，尤其是在绝经前妇女中具有不良预后特征的人群。
