Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression
Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression
复制标题
DOI：
10.1200/jco.2007.14.2471
复制
发表时间：
2008-07-10
影响因子：
45.3
通讯作者：
Blackwell, Kimberly L.
中科院分区：
文献类型：
--
作者：
Anders, Carey K.;Hsu, David S.;Blackwell, Kimberly L.
目的：乳腺癌发生于年轻女性，与低生存率和高阴性临床病理特征发生率相关。生物学驱动这种侵略性疾病尚未被defined.Patients和MethodsClinically注释，从784早期乳腺癌的微阵列数据进行了鉴定，并前瞻性地定义，年龄特异性队列（年轻：= 65岁，n = 211）进行了比较，预后，临床病理变量，mRNA表达值，单基因分析，基因集富集分析（GSEA）。单因素和多因素分析进行了results.ResultsUsing临床病理变量，年轻女性显示较低的雌激素受体（ER）阳性（免疫组化[IHC]，P = .027），较大肿瘤（P = 0.012），较高的人表皮生长因子受体2（HER-2）过表达免疫组化（IHC，P = 0.075）、淋巴结阳性（P = 0.008）、高级别肿瘤（P <0.0001）和无病生存率下降趋势（DFS;风险比= 1.32; P = 0.094）。使用基因组表达分析，年轻女性中出现的肿瘤具有显著较低的ER α mRNA（P < .0001）、ER β（P = .02）和孕酮受体（PR）表达（P < .0001），但HER-2（P < .0001）和表皮生长因子受体（EGFR）表达（P < .0001）较高。探索性分析（GSEA）揭示了367个生物学相关基因集，可显著区分年轻女性中出现的乳腺肿瘤。结合临床病理学和基因组变量之间的肿瘤发生在年轻女性表明，年轻的年龄和较低的ER β和较高的EGFR mRNA表达是显着的预测因素较差的DFS.ConclusionThis大规模的基因组分析表明，乳腺癌发生在年轻女性是一个独特的生物实体驱动的统一致癌信号通路，其特点是激素敏感性较低，HER-2/EGFR表达较高，值得进一步研究，为这一预后不良的妇女群体提供更好的预防和治疗选择。
PurposeBreast cancer arising in young women is correlated with inferior survival and higher incidence of negative clinicopathologic features. The biology driving this aggressive disease has yet to be defined.Patients and MethodsClinically annotated, microarray data from 784 early-stage breast cancers were identified, and prospectively defined, age-specific cohorts (young: = 65 years, n = 211) were compared by prognosis, clinicopathologic variables, mRNA expression values, single-gene analysis, and gene set enrichment analysis (GSEA). Univariate and multivariate analyses were performed.ResultsUsing clinicopathologic variables, young women illustrated lower estrogen receptor (ER) positivity (immunohistochemistry [IHC], P = .027), larger tumors (P = .012), higher human epidermal growth factor receptor 2 (HER-2) overexpression (IHC, P = .075), lymph node positivity (P = .008), higher grade tumors (P < .0001), and trends toward inferior disease-free survival (DFS; hazard ratio = 1.32; P = .094). Using genomic expression analysis, tumors arising in young women had significantly lower ER alpha mRNA (P < .0001), ER beta (P = .02), and progesterone receptor (PR) expression (P < .0001), but higher HER-2 (P < .0001) and epidermal growth factor receptor (EGFR) expression (P < .0001). Exploratory analysis (GSEA) revealed 367 biologically relevant gene sets significantly distinguishing breast tumors arising in young women. Combining clinicopathologic and genomic variables among tumors arising in young women demonstrated that younger age and lower ER beta and higher EGFR mRNA expression were significant predictors of inferior DFS.ConclusionThis large-scale genomic analysis illustrates that breast cancer arising in young women is a unique biologic entity driven by unifying oncogenic signaling pathways, is characterized by less hormone sensitivity and higher HER-2/EGFR expression, and warrants further study to offer this poor-prognosis group of women better preventative and therapeutic options.