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患有激素 受体阳性(HR+)乳腺癌对新辅助内分泌治疗有反应。缺乏 对每个患者乳腺癌内分泌敏感性的直接了解阻碍了最佳的， 量身定做的治疗。如果没有更个性化的方法，许多女性和男性将继续 目前乳腺癌的发病率和死亡率都很高。《公约》的总体目标 拟议的临床试验是调查定量、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 到新辅助内分泌治疗。长期目标是开发功能成像 直接测试乳腺癌患者内分泌治疗对肿瘤敏感性的方法 个体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控靶基因表达的早期变化 内分泌敏感性：孕酮受体(PR)，使用以孕激素为基础的放射性配体，21- [18F]氟尿嘧啶孕酮(FFNP)和定量同步乳腺正电子 发射断层扫描/磁共振成像(PET/MRI)。中心假设是 原发性乳腺肿瘤对FFNP摄取的动态变化与术前治疗的关系 内分泌治疗，它将与治疗反应相关，并超越固有技术 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。 新诊断为ER+/PR+/HER2-浸润性乳腺癌的患者将同时接受 术前短程内分泌治疗前后乳房FFNP的PET/MRI 切除。这项研究的目的是确定1)FFNP PET/MRI预测疗效的有效性 2)FFNP乳腺PET/MRI定量的可靠性。这个 拟议的研究是创新的，因为它将使用功能成像同时进行乳房 PET/MRI提高新辅助内分泌治疗的成功率。影像治疗--诱导 使用FFNP PET/MRI，雌激素调节的信号事件的变化将有显著的意义 通过以下途径实现内分泌治疗反应的早期评估产生积极影响 在使用常规技术测量肿瘤大小的变化之前 乳房X光检查，超声波和触诊。一旦得到验证，这种方法就很容易 结合原发性HR+乳腺癌患者的术前评估 个体化新辅助和辅助治疗计划，以改善患者预后。

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.