Impact of ErbB2 and RB Pathways on DCIS Progression and Treatment

ErbB2 和 RB 通路对 DCIS 进展和治疗的影响

• 批准号: 8373100
• 负责人: Agnieszka Witkiewicz
• 金额: $ 0.9万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-16 至 2012-11-25
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8373100
• 关键词: Accounting; Adjuvant; Adjuvant Therapy; Automobile Driving; Breast Carcinoma; Breast-Conserving Surgery; Carcinoma; Clinical; Clinical Data; Clinical Trials; Comedo; Consensus; Cytotoxic Chemotherapy; Data; Diagnosis; Disease; Disease Progression; Disease model; Estrogen receptor negative; Exhibits; Gene Amplification; In Situ Lesion; Incidence; Intervention; Knowledge; Left; Life; Loss of Heterozygosity; Mammary Neoplasms; Modeling; Molecular Profiling; Newly Diagnosed; Noninfiltrating Intraductal Carcinoma; Operative Surgical Procedures; Outcome; Pathway interactions; Patients; Phenotype; Population; Pre-Clinical Model; Prognostic Marker; Publishing; Radiation; Radiation therapy; Recurrence; Reporting; Role; Screening procedure; Stratification; Testing; Therapeutic; Tumor Suppressor Genes; Woman; base; cohort; experience; high risk; improved; insight; malignant breast neoplasm; mammary epithelium; overexpression; pre-clinical; prognostic; response; tumor

DESCRIPTION (provided by applicant): Currently ductal carcinoma in situ (DCIS) accounts for 20-30% of newly diagnosed breast cancers in screened populations. Because of the inability to stratify the DCIS populations at high risk for recurrence and disease progression, many women are currently over-treated and approximately 10-15% patients have disease recurrence despite surgical and adjuvant interventions. Preliminary and published data indicate that a large fraction of DCIS lesions exhibits alterations in the ErbB2 and RB-pathways. However there are no studies investigating effects of both pathways abnormalities in the same DCIS lesion. In this application we using functional studies, will: 1. Define role of RB pathway in progression of ErbB2 overexpressing DCIS and 2. Determine how RB and ErbB2 status impacts response to radiation therapy. PUBLIC HEALTH RELEVANCE: By improving our understating of mechanism driving progression of DCIS to invasive breast cancer the proposed studies will allow for better prognostic stratification of DCIS patients. Additionally we will investigate approaches to treat DCIS rationally based on knowledge of RB and ErbB2 pathways.

描述（由申请人提供）：目前，在筛查人群中，导管原位癌 (DCIS) 占新诊断乳腺癌的 20-30%。由于无法对复发和疾病进展高风险的 DCIS 人群进行分层，许多女性目前受到过度治疗，尽管进行了手术和辅助干预，但大约 10-15% 的患者仍出现疾病复发。初步和已发表的数据表明，很大一部分 DCIS 病变表现出 ErbB2 和 RB 通路的改变。然而，尚无研究调查同一 DCIS 病变中两种途径异常的影响。在此应用中，我们使用功能研究，将： 1. 定义 RB 通路在 ErbB2 过表达 DCIS 进展中的作用，以及 2. 确定 RB 和 ErbB2 状态如何影响对放射治疗的反应。 公共卫生相关性：通过改进我们对 DCIS 进展为浸润性乳腺癌的机制的理解，拟议的研究将有助于对 DCIS 患者进行更好的预后分层。此外，我们将根据 RB 和 ErbB2 途径的知识研究合理治疗 DCIS 的方法。