Estrogen Receptor Positive Breast Cancer and Therapy

雌激素受体阳性乳腺癌和治疗

• 批准号: 6984632
• 负责人: DAVID A. MANKOFF
• 金额: $ 9.76万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-10 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6984632
• 关键词: aromatase; breast neoplasms; clinical research; enzyme inhibitors; estradiol; estrogen receptors; female; hormone binding protein; hormone metabolism; hormone regulation /control mechanism; hormone related neoplasm /cancer; human subject; human therapy evaluation; image guided surgery /therapy; neoplasm /cancer therapy; patient oriented research; positron emission tomography; prognosis; radionuclides; receptor expression; tissue /cell culture; women' s health

This is an ongoing project in clinical research in breast cancer with the long-term goal of improving hormonal treatment of breast cancer. The principal imaging tool for this Project will continue to be PET ER imaging using [F-18]-fluoroestradiol (FES), and the proposed studies follow directly from our work in the current funding period showing heterogeneous ER expression in breast tumors. We will now test approaches to evaluate factors affecting response. The focus of our proposed studies will be patients with recurrent or metastatic breast cancer from an ER+ primary tumor who are being considered for treatment with aromatase inhibitors, the hormonal therapy of choice for this patient population. In this group of patients, where biopsy is difficult because of multiple or inaccessible sites of disease, imaging can identify therapeutic targets and play a significant role in directing therapy. Our specific aims are to (1) determine the ability of FES PET imaging to predict patient's response to hormonal therapy, (2) determine the early response to hormonal therapy by measuring the change in receptor occupancy and tumor proliferation early in the course of treatment, and (3) determine the relationship between ER expression and the abnormal expression of other growth factor receptors, specifically HER2 and EGFR, and their relationship to response to hormonal therapy. These studies will lead directly to clinical paradigms using PET imaging data with tumor-specific receptor ligands to make individualized choices of therapy in patients. The studies will also identify which mechanisms of resistance to hormonal therapy are clinically important and help direct efforts to overcome resistance to hormonal treatment of breast cancer.

这是一个正在进行的乳腺癌临床研究项目，长期目标是改善乳腺癌的激素治疗。该项目的主要成像工具将继续是使用[F-18]-氟雌二醇（FES）的PET ER成像，并且拟议的研究直接遵循我们在当前资助期内的工作，显示乳腺肿瘤中的异质性ER表达。我们现在将测试评估影响反应的因素的方法。我们建议的研究重点将是考虑用芳香化酶治疗的ER+原发性肿瘤复发或转移性乳腺癌患者 抑制剂，激素治疗的选择，这一患者群体。在这组患者中，由于多个或难以接近的疾病部位，活检是困难的，成像可以识别治疗靶点，并在指导治疗中发挥重要作用。我们的具体目标是（1）确定FES PET成像预测患者对激素治疗反应的能力，（2）通过测量治疗过程早期受体占用和肿瘤增殖的变化来确定对激素治疗的早期反应，以及（3）确定ER表达与其他生长因子受体（特别是HER 2和EGFR）异常表达之间的关系，以及它们对荷尔蒙的反应 疗法这些研究将直接导致临床范例，使用PET成像数据与肿瘤特异性受体配体，使患者的治疗个性化的选择。这些研究还将确定哪些对激素治疗的耐药机制在临床上很重要，并有助于直接努力克服对乳腺癌激素治疗的耐药。