Elucidating Prognosis and Biology of Breast Cancer Arising in Young Women Using Gene Expression Profiling
Elucidating Prognosis and Biology of Breast Cancer Arising in Young Women Using Gene Expression Profiling
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DOI：
10.1158/1078-0432.ccr-11-2599
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发表时间：
2012-03-01
影响因子：
11.5
通讯作者：
Loi, Sherene
中科院分区：
文献类型：
--
作者：
Azim, Hatem A., Jr.;Michiels, Stefan;Loi, Sherene
目的：年轻女性乳腺癌预后差。我们的目的是确定基因表达特征在预测年轻女性预后中的作用，并了解根据年龄的生物学差异。实验设计：使用三基因分类器将患者分配到分子亚型[雌激素受体（ER）（+）/HER 2（-）; HER 2（+），ER-/HER 2（-）]。我们评估了先前发表的增殖、间质和免疫相关的基因特征是否为Adjuvant！并在考克斯模型中测试了他们与年龄的相互作用，以获得无复发生存期（RFS）。此外，我们评估了候选年龄相关基因或基因集与年龄的调整线性回归model.Results：共3,522例患者（20个数据集）之间的关联。40岁及以下患者ER-/HER 2（-）肿瘤比例较高（P < 0.0001），在调整乳腺癌亚型、肿瘤大小、淋巴结状态和组织学分级以及数据集和治疗方式分层后，RFS较差（HR = 1.34，95% CI 1.10-1.63，P = 0.004）。在ER+/HER 2（-）肿瘤中，在调整佐剂后，增殖基因特征与年龄无显著相互作用。网上进一步的分析表明，年轻人的乳腺癌富含与未成熟乳腺上皮细胞（管腔祖细胞，乳腺干细胞，c-kit，RANKL）和生长因子信号传导相关的过程，在两个独立的cohort（n = 1，188和2，334）。然而，年轻时发生的乳腺癌似乎在亚型分布之外具有生物学上的独特性。因此，可能需要单独的治疗方法，如靶向RANKL或乳腺干细胞。临床癌症研究; 18（5）; 1341-51。（C）2012年AACR。
Purpose: Breast cancer in young women is associated with poor prognosis. We aimed to define the role of gene expression signatures in predicting prognosis in young women and to understand biological differences according to age.Experimental Design: Patients were assigned to molecular subtypes [estrogen receptor (ER)(+)/HER2(-); HER2(+), ER-/HER2(-))] using a three-gene classifier. We evaluated whether previously published proliferation, stroma, and immune-related gene signatures added prognostic information to Adjuvant! online and tested their interaction with age in a Cox model for relapse-free survival (RFS). Furthermore, we evaluated the association between candidate age-related genes or gene sets with age in an adjusted linear regression model.Results: A total of 3,522 patients (20 data sets) were eligible. Patients aged 40 years or less had a higher proportion of ER-/HER2(-) tumors (P < 0.0001) and were associated with poorer RFS after adjustment for breast cancer subtype, tumor size, nodal status, and histologic grade and stratification for data set and treatment modality (HR = 1.34, 95% CI 1.10-1.63, P = 0.004). The proliferation gene signatures showed no significant interaction with age in ER+/HER2(-) tumors after adjustment for Adjuvant! online. Further analyses suggested that breast cancer in the young is enriched with processes related to immature mammary epithelial cells (luminal progenitors, mammary stem, c-kit, RANKL) and growth factor signaling in two independent cohorts (n = 1,188 and 2,334).Conclusions: Proliferation-related prognostic gene signatures can aid treatment decision-making for young women. However, breast cancer arising at a young age seems to be biologically distinct beyond subtype distribution. Separate therapeutic approaches such as targeting RANKL or mammary stem cells could therefore be needed. Clin Cancer Res; 18(5); 1341-51. (C)2012 AACR.