Differences in risk factors for breast cancer molecular subtypes in a population-based study
Differences in risk factors for breast cancer molecular subtypes in a population-based study
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DOI：
10.1158/1055-9965.epi-06-0806
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发表时间：
2007-03-01
影响因子：
3.8
通讯作者：
Garcia-Closas, Montserrat
中科院分区：
文献类型：
--
作者：
Yang, Xiaohong R.;Sherman, Mark E.;Garcia-Closas, Montserrat
基因表达数据的分析表明，乳腺癌可分为具有不同临床特征的分子亚型。本研究评估了分子亚型之间的病理特征和病因学关联是否不同。我们评估了参与波兰乳腺癌研究的804名浸润性乳腺癌妇女和2，502名对照。采用免疫组化方法检测雌激素受体α、孕激素受体、人表皮生长因子受体（HER 2和HER 1）和细胞角蛋白5，将病例分为5种分子亚型：管腔型A、管腔型B。HER 2表达、基底细胞样和未分类。使用调整的比值比和95%置信区间估计相对风险。我们观察到，与主要的管腔A型肿瘤（69%）相比，其他亚型在诊断时与不利的临床特征相关，尤其是HER 2表达（8%）和基底样（12%）肿瘤。增加体重指数可显著降低绝经前妇女发生管腔A型肿瘤的风险（比值比，0.71; 95%置信区间，每增加5个单位，0.57-0.88），但不能降低基底细胞样肿瘤的风险（1.18; 0.86-1.64; P-异质性= 0.003）。另一方面，与初潮年龄增加相关的风险降低，基底细胞样肿瘤（每2年增加0.78; 0.68-0.89）比管腔A型肿瘤（0.90; 0.95-1.08; P异质性= 0.0009）更强。尽管家族史增加了所有亚型的风险（未分类的肿瘤除外），但基底细胞样肿瘤的相对风险最高。这项研究的结果表明，乳腺癌的危险因素可能会因表达研究中确定的分子亚型而异，这表明乳腺癌的病因，除了临床，异质性。
Analysis of gene expression data suggests that breast cancers are divisible into molecular subtypes which have distinct clinical features. This study evaluates whether pathologic features and etiologic associations differ among molecular subtypes. We evaluated 804 women with invasive breast cancers and 2,502 controls participating in a Polish Breast Cancer Study. Immunohistochemical stains for estrogen receptor alpha, progesterone receptor, human epidermal growth factor receptors (HER2 and HER1), and cytokeratin 5 were used to classify cases into five molecular subtypes: luminal A, luminal B. HER2-expresing, basal-like, and unclassified. Relative risks were estimated using adjusted odds ratios and 95% confidence intervals. We observed that compared with the predominant luminal A tumors (69%), other subtypes were associated with unfavorable clinical features at diagnosis, especially HER2-expressing (8%) and basal-like (12%) tumors. Increasing body mass index significantly reduced the risk of luminal A tumors among premenopausal women (odds ratios, 0.71; 95% confidence intervals, 0.57-0.88 per five-unit increase), whereas it did not reduce risk for basal-like tumors (1.18; 0.86-1.64; P-heterogeneity = 0.003). On the other hand, reduced risk associated with increasing age at menarche was stronger for basal-like (0.78; 0.68-0.89 per 2-year increase) than luminal A tumors (0.90; 0.95-1.08; Pheterogeneity = 0.0009). Although family history increased risk for all subtypes (except for unclassified tumors), the magnitude of the relative risk was highest for basal-like tumors. Results from this study have shown that breast cancer risk factors may vary by molecular subtypes identified in expression studies, suggesting etiologic, in addition to clinical, heterogeneity of breast cancer.