绝经后管腔型、HER-2过表达型及三阴性乳腺癌的生殖和激素风险因素。
Reproductive and hormonal risk factors for postmenopausal luminal, HER-2-overexpressing, and triple-negative breast cancer.
作者信息
Phipps Amanda I, Malone Kathleen E, Porter Peggy L, Daling Janet R, Li Christopher I
机构信息
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.
出版信息
Cancer. 2008 Oct 1;113(7):1521-6. doi: 10.1002/cncr.23786.
BACKGROUND
Molecular profiling studies have identified subtypes of breast cancer that can be approximately classified by estrogen receptor (ER), progesterone receptor (PR), and HER-2/neu (HER-2) expression. These molecular subtypes are prognostically significant, but to the authors' knowledge, differences in their etiologic profiles have not been established. Reproductive factors may plausibly be differentially correlated with the risk of different breast cancer subtypes because these factors are presumed to impact exposure to endogenous sex hormones.
METHODS
The authors pooled 2 population-based, case-control studies of breast cancer in women ages 55 to 79 years for an analysis including 1476 controls and 1023 cases of luminal breast cancer, 39 cases of HER-2-overexpressing breast cancer, and 78 cases of triple-negative breast cancer. Polytomous logistic regression was used to compare each case group with controls.
RESULTS
Associations varied by molecular subtype. Early age at menarche was only found to be associated with risk of HER-2-overexpressing disease (odds ratio [OR] of 2.7; 95% confidence interval [95% CI], 1.4-5.5), whereas breastfeeding for > or =6 months was only found to be protective for luminal and triple-negative disease (OR of 0.8 [95% CI, 0.6-1.0] and OR of 0.5 [95% CI, 0.3-0.9], respectively). Both late age at menopause and the use of estrogen plus progestin hormone therapy were only found to be associated with risk of luminal disease (OR of 1.6 [95% CI, 1.1-2.2] and OR of 1.7 [95% CI, 1.3-2.1], respectively). No differences in risks associated with parity or age at first live birth were observed by subtype.
CONCLUSIONS
Certain reproductive factors may have a greater impact on the risk of certain molecular subtypes of disease compared with others. Future studies that further define the etiology of breast cancer subtypes will add to the biologic understanding of this disease.
背景
分子谱分析研究已确定了乳腺癌的亚型，这些亚型可大致根据雌激素受体（ER）、孕激素受体（PR）和HER-2/neu（HER-2）表达进行分类。这些分子亚型具有预后意义，但据作者所知，它们病因学特征的差异尚未明确。生殖因素可能与不同乳腺癌亚型的风险存在不同程度的相关性，因为这些因素被认为会影响内源性性激素的暴露。
方法
作者汇总了两项基于人群的55至79岁女性乳腺癌病例对照研究，分析纳入了1476名对照以及1023例管腔型乳腺癌、39例HER-2过表达型乳腺癌和78例三阴性乳腺癌病例。采用多分类逻辑回归将每个病例组与对照组进行比较。
结果
关联因分子亚型而异。初潮年龄早仅与HER-2过表达型疾病风险相关（比值比[OR]为2.7；95%置信区间[95%CI]，1.4 - 5.5），而母乳喂养≥6个月仅对管腔型和三阴性疾病具有保护作用（OR分别为0.8[95%CI，0.6 - 1.0]和0.5[95%CI，0.3 - 0.9]）。绝经年龄晚和使用雌激素加孕激素激素治疗均仅与管腔型疾病风险相关（OR分别为1.6[95%CI，1.1 - 2.2]和1.7[95%CI，1.3 - 2.1]）。各亚型在与产次或首次生育年龄相关的风险方面未观察到差异。
结论
某些生殖因素对某些疾病分子亚型风险的影响可能比其他因素更大。进一步明确乳腺癌亚型病因的未来研究将增进对该疾病的生物学理解。
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