Precision Imaging of Breast Cancer for Guiding Neoadjuvant Endocrine Therapy

迫切需要准确的非侵入性生物标志物来识别哪些患者激素 受体阳性（HR+）乳腺癌将响应于新辅助内分泌治疗。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的， 量身定制的治疗如果没有更个性化的方法，许多女性和男性将继续 受目前乳腺癌发病率和死亡率的影响。的总体目标 拟议的临床试验是调查定量的能力，混合功能成像， 评估激素敏感性、雌激素受体（ER）功能抑制和早期反应 新辅助内分泌治疗长期目标是发展功能成像 在乳腺癌患者中直接测试肿瘤对内分泌治疗的敏感性的方法， 个性化的治疗计划和改善的结果。拟议的研究将调查 作为替代指标的经典雌激素调节靶基因表达的早期变化 内分泌敏感性：孕激素受体（PR）使用孕激素为基础的放射性配体，21- [18F]氟呋喃甲孕酮（FFNP）和定量同步乳腺正电子 发射断层扫描/磁共振成像（PET/MRI）。核心假设是， 原发性乳腺肿瘤的FFNP摄取将显示对术前化疗的动态变化。 内分泌治疗，这将与治疗反应，并超过固有的技术 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 新诊断的ER+/PR+/HER 2浸润性乳腺癌患者，将接受同时 手术前短期内分泌治疗前后使用FFNP进行乳腺PET/MRI检查 切除本研究旨在确定1）FFNP PET/MRI预测缓解的有效性 术前内分泌治疗和2）FFNP乳腺PET/MRI的定量可靠性。的 拟议的研究是创新的，因为它将使用功能成像与同时乳房 PET/MRI可提高新辅助内分泌治疗的成功率。成像治疗诱导 使用FFNP PET/MRI，雌激素调节的信号传导事件的变化将具有显著的 通过早期评估内分泌治疗反应， ER在肿瘤大小变化之前可以使用常规技术测量，例如 乳房X光检查超声波和触诊一旦验证，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， 个体化新辅助和辅助治疗计划，以改善患者结局。

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.