Precision Imaging of Breast Cancer for Guiding Neoadjuvant Endocrine Therapy

乳腺癌精确成像指导新辅助内分泌治疗

• 批准号: 10707285
• 负责人: Amy Fowler
• 金额: $ 60.09万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-20 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10707285
• 关键词: Adjuvant Chemotherapy; Adjuvant Therapy; Aftercare; Agreement; Axilla; Biological; Biological Markers; Breast; Breast Cancer Patient; Breast-Conserving Surgery; Clinical; Clinical Trials; Data; Diffusion; ERBB2 gene; Endocrine; Enrollment; Estrogen Receptors; Estrogens; Evaluation; Event; Excision; Functional Imaging; Genes; Goals; Hormonal; Hybrids; Image; Knowledge; Magnetic Resonance Imaging; Mammary Neoplasms; Mammography; Measures; Mediating; Metastatic breast cancer; Metastatic/Recurrent; Methods; Mission; Modality; Morbidity - disease rate; Multicenter Trials; Mutation; Neoadjuvant Therapy; Newly Diagnosed; Operative Surgical Procedures; Outcome; Palpation; Patient-Focused Outcomes; Patients; Perfusion; Phase; Phase II Clinical Trials; Physicians; Positron-Emission Tomography; Pre-Clinical Model; Prediction of Response to Therapy; Predictive Value; Prior Therapy; Progesterone Receptors; Progestins; Proliferating; Protocols documentation; Reader; Reference Standards; Research; Resistance; Safety; Scanning; Signal Transduction; Staging; Techniques; Testing; Translating; Treatment Efficacy; Treatment outcome; Tumor Burden; Tumor Markers; United States National Institutes of Health; Woman; Work; X-Ray Computed Tomography; Xenograft procedure; adjuvant endocrine therapy; antagonist; breast imaging; care outcomes; chemotherapy; deprivation; drug sensitivity; efficacy evaluation; hormone receptor-positive; hormone therapy; imaging agent; imaging approach; imaging modality; improved; improved outcome; in vivo; individualized medicine; innovation; malignant breast neoplasm; men; molecular subtypes; mortality; multiparametric imaging; novel diagnostics; personalized approach; personalized care; phase 2 study; pre-clinical; precision medicine; predicting response; prospective; quantitative imaging; radioligand; receptor; receptor expression; resistance mechanism; response; standard of care; success; tool; treatment optimization; treatment planning; treatment response; tumor; tumor growth; tumor xenograft; ultrasound; uptake

Accurate non-invasive biomarkers are urgently needed to identify which patients with hormone receptor positive (HR+) breast cancer will respond to neoadjuvant endocrine therapy. Lack of direct knowledge of the endocrine sensitivity of each patient’s breast cancer impedes optimal, tailored therapy. Without a more personalized approach, many women and men will continue to suffer from the current morbidity and mortality of breast cancer. The overall objective of the proposed clinical trial is to investigate the ability of quantitative, hybrid functional imaging for assessing hormonal sensitivity, estrogen receptor (ER) functional inhibition, and early response to neoadjuvant endocrine therapy. The long-term goal is to develop functional imaging approaches to directly test tumor sensitivity to endocrine therapy in breast cancer patients for individualized treatment plans and improved outcomes. The proposed research will investigate early changes in expression of a classic estrogen-regulated target gene as a surrogate measure of endocrine sensitivity: progesterone receptor (PR) using a progestin-based radioligand, 21- [18F]fluorofuranylnorprogesterone (FFNP) and quantitative simultaneous breast positron emission tomography/magnetic resonance imaging (PET/MRI). The central hypothesis is that FFNP uptake in primary breast tumors will show dynamic changes in response to presurgical endocrine therapy, which will correlate with treatment response and exceed inherent technical variability. The proposed clinical trial is a prospective, single-center study that will enroll women with newly diagnosed ER+/PR+/HER2- invasive breast cancer who will undergo simultaneous breast PET/MRI with FFNP before and after a short course of endocrine therapy prior to surgical excision. The study aims to determine 1) the efficacy of FFNP PET/MRI for predicting response to presurgical endocrine therapy and 2) the quantitative reliability of FFNP breast PET/MRI. The proposed research is innovative because it will use functional imaging with simultaneous breast PET/MRI to improve the success of neoadjuvant endocrine therapy. Imaging treatment-induced changes in estrogen-regulated signaling events, using FFNP PET/MRI, will have a significant positive impact by enabling early assessment of endocrine therapy response mediated through ER before changes in tumor size can be measured using conventional techniques such as mammography, ultrasound, and palpation. Once validated, this approach can easily be integrated into the preoperative evaluation of patients with primary HR+ breast cancer to individualize neoadjuvant and adjuvant treatment plans for improved patient outcomes.

迫切需要准确的非侵入性生物标志物来识别哪些患者患有激素 受体阳性（HR+）乳腺癌将对新辅助内分泌治疗有反应。缺乏 直接了解每位患者乳腺癌的内分泌敏感性会阻碍最佳、 量身定制的治疗。如果没有更加个性化的方法，许多女性和男性将继续 患有当前乳腺癌的发病率和死亡率。总体目标 拟议的临床试验旨在研究定量、混合功能成像的能力 评估激素敏感性、雌激素受体 (ER) 功能抑制和早期反应 至新辅助内分泌治疗。长期目标是开发功能成像 直接测试乳腺癌患者肿瘤对内分泌治疗敏感性的方法 个性化的治疗计划和改善的结果。拟议的研究将调查 经典雌激素调节靶基因表达的早期变化作为替代措施 内分泌敏感性：使用基于孕激素的放射性配体的孕激素受体（PR），21- [18F]氟呋喃去甲孕酮 (FFNP) 和同步定量乳腺正电子 发射断层扫描/磁共振成像 (PET/MRI)。中心假设是 原发性乳腺肿瘤中 FFNP 的摄取将随术前表现出动态变化 内分泌治疗，这将与治疗反应相关并超越固有的技术 可变性。拟议的临床试验是一项前瞻性、单中心研究，将招募女性 新诊断为 ER+/PR+/HER2- 浸润性乳腺癌的患者将同时接受 手术前短期内分泌治疗前后使用 FFNP 进行乳房 PET/MRI 检查 切除。该研究旨在确定 1) FFNP PET/MRI 预测反应的功效 2) FFNP 乳腺 PET/MRI 的定量可靠性。这 拟议的研究具有创新性，因为它将使用同步乳房功能成像 PET/MRI 可提高新辅助内分泌治疗的成功率。影像学治疗诱导 使用 FFNP PET/MRI，雌激素调节信号事件的变化将产生显着的影响 通过对内分泌治疗反应进行早期评估来产生积极影响 可以使用常规技术测量肿瘤大小变化之前的 ER，例如 乳房X光检查、超声波和触诊。一旦经过验证，这种方法可以很容易地 纳入原发性 HR+ 乳腺癌患者的术前评估 个性化新辅助和辅助治疗计划，以改善患者的预后。