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.

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