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，拟议的研究直接源于我们在当前资助期间的工作，显示乳腺肿瘤中的异质 ER 表达。我们现在将测试评估影响反应因素的方法。我们提议的研究重点是患有 ER+ 原发肿瘤的复发性或转移性乳腺癌患者，这些患者正在考虑接受芳香酶治疗 抑制剂，该患者群体的首选激素疗法。在这组患者中，由于疾病部位较多或难以接近，活检很困难，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据和肿瘤增殖的变化来确定对激素治疗的早期反应， (3) 确定 ER 表达与其他生长因子受体（特别是 HER2 和 EGFR）异常表达之间的关系，以及它们与激素反应的关系 治疗。这些研究将直接产生使用 PET 成像数据和肿瘤特异性受体配体的临床范例，为患者做出个体化的治疗选择。这些研究还将确定哪些激素治疗耐药机制在临床上具有重要意义，并有助于指导克服乳腺癌激素治疗耐药性的努力。