Mammographic Density and Metabolic Genotyping for Predicting Cancer Prognosis

用于预测癌症预后的乳房 X 线摄影密度和代谢基因分型

• 批准号: 9376399
• 负责人: Jeon-Hor Chen
• 金额: $ 20.16万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9376399
• 关键词: Adjuvant; Adverse effects; Affect; Affinity; Alleles; Antineoplastic Protocols; Archives; Area; Aromatase Inhibitors; Biological Markers; Blood; Blood specimen; Breast; Breast Cancer Patient; CYP2D6 gene; Cancer Prognosis; Caring; Cessation of life; Chemoprevention; Chinese People; Confounding Factors (Epidemiology); Consent; Contralateral; Cytochrome P450; Data; Databases; Development; Diagnosis; Diagnostic; Disease; Disease-Free Survival; Distant Metastasis; Ensure; Enzymes; Estrogen Antagonists; Estrogen Receptors; Failure; Formalin; General Hospitals; Genes; Genetic Status; Genotype; Goals; High Risk Woman; Hormonal; Hospitals; Image; Individual; Institution; Koreans; Magnetic Resonance Imaging; Malignant Neoplasms; Mammographic Density; Mammography; Measures; Mediating; Metabolic; Metabolism; Methods; Monitor; Newly Diagnosed; Odds Ratio; Operative Surgical Procedures; Paraffin Embedding; Patient Care; Patients; Perimenopause; Persons; Pharmaceutical Preparations; Postmenopause; Premenopause; Prognostic Factor; Progressive Disease; Prospective Studies; Radiation; Recording of previous events; Recurrence; Registries; Research; Resolution; Resources; Risk; Risk Factors; Role; Staging; Subgroup; Surrogate Markers; Sweden; TNM; Taiwan; Tamoxifen; Tissues; Treatment Efficacy; Treatment Protocols; Treatment outcome; Veterans; Visit; Woman; XCL1 gene; base; breast density; cancer recurrence; cancer risk; chemotherapy; cohort; cost; density; design; follow-up; genetic analysis; genetic variant; hormone therapy; improved; inclusion criteria; individual patient; interest; malignant breast neoplasm; melting; molecular marker; outcome forecast; prognostic; prognostic value; randomized placebo controlled trial; receptor; response; standard of care; success

ABSTRACT Title: Mammographic Density and Metabolic Genotyping for Predicting Cancer Prognosis This project will investigate the role of quantitative mammographic density (MD) and cytochrome P450 CYP2D6 metabolic genotyping in the prognosis of breast cancer (BC) patients, with the ultimate goal of using them as prognostic predictors for improving the treatment that can be provided to each individual patient. Mammographic density is an established risk factor for developing breast cancer, and there is also evidence suggesting that cancers arising from dense tissue area are more aggressive; therefore collectively they suggest MD may serve as a prognostic predictor. In this project we will utilize a single-institution, all- Chinese, patient cohort that is treated in one hospital using similar strategies (Taichung Veteran's General Hospital in Taiwan). Their Breast Care Center has established a detailed registry, and each patient's personal factors, TNM staging, molecular biomarkers, imaging findings, and treatment protocols (surgery, radiation, chemotherapy and hormonal therapy) are all well documented in the database. Patients with newly diagnosed Stage I, II, and III invasive breast cancer will be identified from the registry as the inclusion criteria. The majority of patients are continuingly being followed in the same hospital, so it is very easy to find their prognostic information, including development of recurrence, secondary BC, distant metastasis and BC-specific death. This registry provides a great resource for investigating the association of MD with patients' prognosis (Aim-1). For patients diagnosed with hormonal receptor positive BC, it is the standard of care to give them hormonal therapy, e.g. tamoxifen for pre- and peri-menopausal women. Although the treatment has been shown very effective in improving disease-free survival and overall survival on a statistical basis, many patients still develop progressive disease, raising the question of individual responsiveness. The hormonal therapy drugs are associated with various side effects; thus there is a strong interest to find biomarkers that can predict the responsiveness of each individual patient to ensure a favorable benefit-to-risk ratio. MD reduction has been shown as a valid surrogate marker for predicating tamoxifen response, and it would be very interesting to understand why some women would respond and show MD reduction but others not. Aim-2 was designed to predict tamoxifen treatment efficacy based on MD reduction and the CYP2D6 genotyping that are known to affect the metabolism of tamoxifen to active compounds that have a high affinity for estrogen receptors. Patients returning to hospital for in-person follow-up will be invited to provide blood samples for the CYP2D6 genotyping, by using a new method based on the high-resolution melting curve analysis (HRM), which has been validated in Chinese women and proven to be efficient and low-cost. Based on the gene alleles patients will be determined as extensive metabolizers or intermediate metabolizers. The CYP2D6 metabolic status will be correlated with MD reduction, and then both correlated with prognosis. Further, they will be combined to investigate whether these two factors can be added to improve the prediction of prognosis.

抽象的 标题：用于预测癌症预后的乳房X线摄影密度和代谢基因分型 该项目将研究定量乳腺X线摄影密度（MD）和细胞色素P450的作用 CYP2D6乳腺癌预后（BC）患者的代谢基因分型，最终目标是 以它们为预后预测因素，以改善可以提供给每个人的治疗方法 病人。乳腺X线摄影密度是乳腺癌既定的危险因素，也有 证据表明，由致密组织区域引起的癌症更具侵略性。因此集体 他们认为MD可以用作预后预测因子。在这个项目中，我们将利用一个机构 使用类似策略在一家医院接受治疗的中国患者队列 台湾医院）。他们的乳房护理中心已经建立了一个详细的注册表，每个患者的注册表 个人因素，TNM分期，分子生物标志物，成像发现和治疗方案（手术， 辐射，化学疗法和荷尔蒙治疗）在数据库中都有很好的记录。患者 新诊断的I期，II和III侵入性乳腺癌将从注册表中确定为包含 标准。大多数患者在同一家医院继续受到追踪，因此很容易 找到他们的预后信息，包括复发的发展，次要BC，遥远的转移 和特定于卑诗省的死亡。该注册表为调查医学博士协会与 患者的预后（AIM-1）。对于诊断为激素受体阳性BC的患者，它是 谨慎地给予他们荷尔蒙治疗，例如他莫昔芬用于期间和绝经周围的妇女。虽然 治疗已显示在改善无疾病的生存和总体生存方面非常有效 统计基础，许多患者仍会发展为进行性疾病，提出了个体的问题 响应能力。激素治疗药物与各种副作用有关。因此有一个强大的 兴趣找到可以预测每个患者的反应能力的生物标志物，以确保 有利的利益风险比率。减少MD已显示为有效的替代标记物用于鉴定 他莫昔芬的反应，理解为什么有些女性会做出回应和 显示减少MD，但没有显示其他。 AIM-2旨在预测基于 MD还原和CYP2D6基因分型会影响他莫昔芬的代谢为活性 对雌激素受体具有高亲和力的化合物。返回医院亲自的患者 将邀请随访通过使用新方法为CYP2D6基因分型提供血液样本 基于高分辨率熔解曲线分析（HRM），该分析已在中国妇女中得到验证 并被证明是高效且低成本的。基于基因等位基因的患者将被确定为广泛 代谢剂或中间代谢物。 CYP2D6代谢状态将与MD相关 还原，然后均与预后相关。此外，他们将合并以调查是否 可以添加这两个因素以改善预后的预测。