Peripheral Blood Molecular Staging of Breast Cancer

乳腺癌的外周血分子分期

• 批准号: 7669268
• 负责人: William E. Gillanders
• 金额: $ 23.49万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-12 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7669268
• 关键词: Address; Age; American; Benign; Biological Assay; Blood specimen; Breast Cancer Cell; Breast Diseases; Cancer Patient; Caucasoid Race; Characteristics; Clinical; Cohort Studies; Density Gradient Centrifugation; Detection; Development; Diagnostic; Disease; Double-Blind Method; Gene Expression; Genes; Individual; Malignant Neoplasms; Medical; Medicine; Modality; Molecular; Molecular Biology; Molecular Genetics; Monitor; Nucleotides; Outcome; Patients; Process; Protocols documentation; Race; Research; Research Personnel; Reverse Transcriptase Polymerase Chain Reaction; Saints; Sampling; South Carolina; Specimen; Staging; Systemic Therapy; TFF1 gene; Techniques; Technology; Test Result; Time; Treatment Protocols; Universities; Validation; Washington; Woman; base; candidate marker; clinically relevant; cohort; cost; design; experience; healthy volunteer; malignant breast neoplasm; mimetics; molecular marker; neoplastic cell; new technology; novel; outcome forecast; overexpression; peripheral blood; prognostic; programs; prospective; response

DESCRIPTION (provided by applicant): Breast cancer remains the most common cancer among American women, representing an estimated 30% of all new cancer cases in women. The current staging modalities for breast cancer are invasive, expensive, and lack sensitivity, limiting the ability of clinicians to tailor therapies to individual patients. The identification of genes overexpressed in breast cancer combined with recent advances in molecular biology provide the opportunity to establish more sensitive, specific, and potentially cost-effective ways of staging breast cancer. Two new technologies have recently been developed that significantly enhance the ability to detect breast cancer-associated gene overexpression in the peripheral blood: a novel porous barrier density gradient centrifugation technique, and real-time RT-PCR. The hypothesis of the proposed research is that realtime RT-PCR detection of breast cancer cells in the peripheral blood of breast cancer patients is associated with clinical outcome. In Specific Aim 1, Objective 1 we will establish criteria for defining positive molecular test results. To establish rigorous threshold values for marker positivity, we will obtain peripheral blood samples from a cohort of healthy volunteer subjects with no evidence of malignancy. We will determine the background expression of candidate molecular markers in these specimens. We will also determine if the background expression of candidate markers is independent of baseline patient characteristics including age (>50 versus =50), race (White versus Not White) and the presence of benign breast disease (Present versus Absent). In Objective 2, we will design and validate internal positive control gene fragment mimetics to be used as an additional control for the molecular assays. In Specific Aim 2, we will define the clinical relevance of molecular detection of circulating breast cancer cells in a double-blinded prospective cohort study involving 92 subjects at Washington University in Saint Louis and the Medical University of South Carolina. The primary hypothesis is that Stage IV breast cancer patients initiating a new regimen of systemic therapy with molecular evidence of breast cancer in the peripheral blood will experience a decreased 1-year progression-free and overall survival compared to Stage IV breast cancer patients with no molecular evidence of breast cancer in the peripheral blood. Secondary objectives will address the significance of molecular detection of breast cancer cells after the initiation of therapy. Advances in molecular genetics have brought a revolution to medicine; the successful development of a molecular assay for the detection of breast cancer cells in the peripheral blood of breast cancer patients is likely to do the same for those unfortunate women afflicted with this disease.

描述（由申请人提供）： 乳腺癌仍然是美国女性中最常见的癌症，估计占女性所有新发癌症病例的30%。目前乳腺癌的分期方式是侵入性的，昂贵的，缺乏敏感性，限制了临床医生为个体患者定制治疗的能力。在乳腺癌中过表达的基因的鉴定结合分子生物学的最新进展提供了建立更敏感，特异性和潜在的成本效益的乳腺癌分期方法的机会。最近开发了两种新技术，显着提高了检测乳腺癌相关基因在外周血中过度表达的能力：一种新的多孔屏障密度梯度离心技术，和实时RT-PCR。这项研究的假设是，乳腺癌患者外周血中乳腺癌细胞的实时RT-PCR检测与临床结果相关。 在具体目标1，目标1中，我们将建立定义阳性分子检测结果的标准。为了建立标记物阳性的严格阈值，我们将从一组没有恶性肿瘤证据的健康志愿者受试者中获得外周血样本。我们将确定这些标本中候选分子标记的背景表达。我们还将确定候选标志物的背景表达是否独立于基线患者特征，包括年龄（>50与=50）、种族（白色与非白色）和良性乳腺疾病的存在（存在与不存在）。在目标2中，我们将设计并验证内部阳性对照基因片段模拟物，用作分子试验的额外对照。在具体目标2中，我们将在一项双盲前瞻性队列研究中定义循环乳腺癌细胞分子检测的临床相关性，该研究涉及圣刘易斯的华盛顿大学和南卡罗来纳州医科大学的92名受试者。主要假设是，与外周血中没有乳腺癌分子证据的IV期乳腺癌患者相比，外周血中有乳腺癌分子证据的IV期乳腺癌患者开始新的全身治疗方案将经历1年无进展生存期和总生存期的降低。次要目的将解决治疗开始后乳腺癌细胞的分子检测的意义。 分子遗传学的进步给医学带来了一场革命;成功开发了一种用于检测乳腺癌患者外周血中乳腺癌细胞的分子测定法，很可能对那些不幸患有这种疾病的妇女也有同样的作用。