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.

迫切需要精确的非侵入性生物标志物来识别哪些患有骑马的患者 接受者阳性（HR+）乳腺癌将对新辅助内分泌治疗作出反应。缺乏 直接了解每个患者乳腺癌的内分泌敏感性，阻碍了最佳 量身定制的疗法。没有更个性化的方法，许多男女将继续 患有当前的发病率和乳腺癌死亡率。总体目标 拟议的临床试验是研究定量，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 进行新辅助内分泌疗法。长期目标是开发功能成像 直接测试乳腺癌患者内分泌治疗肿瘤敏感性的方法 个性化的治疗计划并改善了结果。拟议的研究将调查 经典雌激素调节的靶基因表达的早期变化作为替代测量 内分泌敏感性：使用基于孕激素的放射性物体21-的孕酮受体（PR） [18F]氟呋喃基烯酸酯（FFNP）和定量同时乳房正电子 发射断层扫描/磁共振成像（PET/MRI）。中心假设是 原发性乳腺肿瘤中的FFNP摄取将显示出动态变化 内分泌疗法将与治疗反应相关并超过继承技术 可变性。拟议的临床试验是一项前瞻性的单中心研究，将招募女性 与新诊断的ER+/PR+/HER2-侵入性乳腺癌一起进行的简单 在短暂的内分泌治疗前后，母乳/MRI在手术之前和之后 切除。该研究旨在确定1）FFNP PET/MRI预测响应的效率 前术内分泌疗法和2）FFNP母乳/MRI的定量可靠性。这 拟议的研究具有创新性，因为它将使用简单的乳房使用功能成像 PET/MRI改善新辅助内分泌疗法的成功。成像处理引起的 使用FFNP PET/MRI的雌激素调节的信号事件的变化将具有显着 通过启用通过早期评估内分泌治疗反应的积极影响 在肿瘤大小变化之前，可以使用常规技术（例如 乳房X线摄影，超声和触诊。一旦得到验证，这种方法很容易 集成到对原发性HR+乳腺癌患者的术前评估中 个性化新辅助，并调整治疗计划，以改善患者结局。