Genomic characterization of breast cancer in high risk subsets of breast cancer

40岁以下的妇女约占乳腺癌患者的5%，但许多研究表明，她们的预后和预后比年龄较大的妇女更差。来自年轻女性的乳腺肿瘤通常是ER阴性的，来自非洲裔美国人的患者，并且具有其他高风险指标：然而，多变量分析表明，年轻本身是预后不良的独立预测因素。至少部分是由于国防部所服务的患者群体的独特性质，在WRNMMC看到年轻女性乳腺癌病例的不成比例。因此，CBCP招募了大量40岁以下的浸润性乳腺癌患者，使我们有可能提出这项研究。位于Windber研究所的CBCP组织库在OCT中有40个肿瘤，这些肿瘤的生殖系DNA可从这些样本的血凝块中获得。因此，有足够的数量来获得有意义的数据。来自年轻患者的肿瘤将使用相同的平台直接与来自老年女性的生物库中的肿瘤进行比较。肿瘤将进行全外显子组测序，RNAseq和蛋白质组学分析。这些分析将使我们能够确定在年轻女性肿瘤中观察到的突变谱。基于肿瘤的临床分类（管腔A、管腔B、HER2+和三阴性），将所有这些样本临床注释为组。对于从WRNMMC入组的患者，大多数病例有结局数据，正在收集更多结局数据。这些分析将与公开可用的乳腺癌数据库（例如TCGA）进行比较，以验证我们数据中年轻和老年队列之间的差异。尽管患有乳腺癌的年轻女性预后不良，但几乎没有研究，也没有临床特异性临床试验。该项目及其进一步发展可能是该领域的一个重大进展。

Women under the age of 40 account for approximately 5% percent of breast cancer patients but numerous studies have shown that they have a worse prognosis and poorer outcome than women diagnosed at older ages. Breast tumors from young women are often ER-negative, from African-American patients and have other indicators of high risk: yet, multivariate analyses demonstrated that young age, in and of itself, is an independent predictor of poor outcome. At least partially due to the unique nature of the patient population served by DOD, a disproportionate number of breast cancer cases in young women are seen at WRNMMC. Thus CBCP has enrolled a good number of invasive breast cancer patients under 40 making it possible for us to propose this study. The CBCP Tissue Bank hosted at the Windber Research Institute has 40 tumors in OCT with germ line DNA available from blood clots for these sample. Thus there are sufficient numbers to get meaningful data. The tumors from young patients will be directly compared to those in the biobank from older women using the same platforms. The tumors will undergo whole exome sequencing, RNAseq, and proteomic analysis. These analyses will allow us to determine the spectrum of mutations seen in tumors from young women. All of these samples are clinically annotated into groups based on the clinical classification of the tumors (Luminal A, Luminal B, HER2+, and triple negative). For patients enrolled from the WRNMMC, most of the cases have outcome data and more outcome data is being collected. These analyses will be compared to the publicly available databases for breast cancer (e.g. TCGA) in order to validate differences between the younger and older cohort in our data. Despite the poor prognosis of young women with breast cancer, little research and no clinical specific clinical trials are available. This project and its further development could represent a major advance in the field.