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

乳腺癌高危亚群中乳腺癌的基因组特征

• 批准号: 10926257
• 负责人: Stanley Lipkowitz
• 金额: $ 19.01万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10926257
• 关键词: African American; Age; Blood coagulation; Breast Cancer Patient; Characteristics; Classification; Clinical; Clinical Trials; DNA; Data; Databases; Development; Diagnosis; ERBB2 gene; Enrollment; Estrogen receptor negative; Genomics; Germ Lines; Mammary Neoplasms; Metaplastic carcinoma of the breast; Multivariate Analysis; Mutation; Nature; Outcome; Patients; Prognosis; Proteomics; Research; Research Institute; Sampling; The Cancer Genome Atlas; Tissue Banks; Woman; biobank; cohort; exome sequencing; high risk; human old age (65+); malignant breast neoplasm; older women; participant enrollment; patient population; public database; transcriptome sequencing; tumor; young woman

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.

40岁以下的女性约占乳腺癌患者的5%，但大量研究表明，与年龄较大的女性相比，她们的预后更差，结果也更差。来自年轻女性的乳腺肿瘤通常为er阴性，来自非裔美国患者，并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子。至少部分原因是由于国防部所服务的患者群体的独特性质，在wnmmc中看到了不成比例的年轻女性乳腺癌病例。因此，CBCP纳入了大量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，这些肿瘤样本可以从血凝块中获得生殖系DNA。因此，有足够的数字来获得有意义的数据。使用相同的平台，年轻患者的肿瘤将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年轻女性肿瘤中所见的突变谱。所有样本均根据肿瘤临床分类（Luminal A、Luminal B、HER2+、三阴性）进行临床注释分组。对于从WRNMMC纳入的患者，大多数病例都有结果数据，并且正在收集更多的结果数据。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。尽管年轻女性乳腺癌的预后较差，但很少有研究，也没有临床特异性临床试验。这个项目及其进一步发展可能是该领域的一个重大进展。

项目成果

First-in-human phase 0 study of 111In-CHX-A"-DTPA trastuzumab for HER2 tumor imaging.

• DOI: 10.15761/jts.1000269
• 发表时间: 2019-04-01
• 期刊: Journal of translational science
• 作者: Kurdziel, K A;Mena, E;Choyke, P L
• 通讯作者: Choyke, P L

Analysis of breast cancer in young women in the Department of Defense (DOD) database.

• DOI: 10.1007/s10549-017-4615-8
• 发表时间: 2018-04
• 期刊: Breast cancer research and treatment
• 影响因子: 3.8
• 作者: Zimmer AS;Zhu K;Steeg PS;Wu A;Gatti-Mays ME;Soltani S;Perkins JG;Shao S;Brown D;Georg M;Hu H;Shriver CD;Lipkowitz S
• 通讯作者: Lipkowitz S

Rare Breast Cancer Subtypes.

• DOI: 10.1007/s11912-021-01048-4
• 发表时间: 2021-03-23
• 期刊: Current oncology reports
• 影响因子: 4.7
• 作者: Jenkins S;Kachur ME;Rechache K;Wells JM;Lipkowitz S
• 通讯作者: Lipkowitz S