A Novel Long-Lived 41Ca Marker To Assess Bone Turnover For Breast Cancer Patients

一种用于评估乳腺癌患者骨转换的新型长效 41Ca 标记物

基本信息

批准号：
7659665
负责人：
Susanta K Hui
金额：
$ 7.33万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-01 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7659665
关键词：
Adjuvant Therapy Aromatase Inhibitors Biological Assay Biological Markers Blood Bone Density Bone Resorption Bone remodeling Breast Cancer Treatment Calcium Cancer Patient Cancer Survivor Clinical Comparative Study Consent DEXA Detection Drug Kinetics Drug Monitoring Dual-Energy X-Ray Absorptiometry Due Process Early Diagnosis Early identification Early treatment Estrogen receptor positive Estrogens Evaluation Experimental Designs Fracture Goals Hormones Hospital Costs Individual Adjustment Intervention Label Life Malignant Neoplasms Measurement Measures Metabolic Methods Monitor NTx telopeptide Osteogenesis Osteoporosis Patient Monitoring Patients Pharmaceutical Preparations Physicians Population Postmenopause Prevention Preventive Principal Investigator Process Quality of life Research Personnel Risk Scanning Screening procedure Serum Staging Survivors Techniques Testing Tracer Treatment Efficacy Urine Woman aging population base bisphosphonate bone bone loss bone turnover cancer therapy comparative high risk improved in vivo innovation intervention effect malignant breast neoplasm novel prevent programs research study response tool treatment response tumor progression urinary

项目摘要

DESCRIPTION (provided by applicant): Breast cancer is the most common cancer in women. With growing numbers of breast cancer survivors, cancer treatment induced bone loss and bone fracture are becoming a major concern. Aromatase inhibitor (AI) is very succesful as an adjuvant therapy in estrogen positive postmenopausal women to prevent cancer progression. However, it also increases bone loss and suceptibility to fractures due to profound estrogen depletion. Early identification of patients at a high risk for bone loss, prevention, and frequent monitoring of treatment interventions are absolutely necessary to decrease the risk of bone fractures. The currently much-used method of monitoring bone mineral density (BMD) is neither sensitive to small changes in bone density, nor suitable for frequent assesments of bone density. We propose an innovative assay method to directly detect early changes in bone turnover, to be used for long-term monitoring purposes. We hypothesize that the 41Ca/Ca measurement in urine will offer (a) early detection of the accelerated bone resorption that result from the use of aromatase inhibitors, and (b) dynamic monitoring of the bone formation process due to antiresorptive drug intervention. Specific Aims:To determine the AI treatment response in pharmacokinetics (PK) of long-lived 41Ca and compare with BMD measurements, urine NTx levels, and serum PINP levels. To use the 41Ca assay to monitor the effects of bisphosphonate intervention on bone formation and to compare this to BMD measurements, urine NTx levels, and serum PINP levels. A microdose amount of 41Ca will be administered intravenously to all consented postmenopausal breast cancer patients. The urinary 41Ca assay will be characterized with and without AI interventionto establish the enhanced bone resorption in postmenopausal breast cancer patients. This assay will be further compared to DXA scans, urine NTx levels, serum PINP levels. PTH, complete blood metabolic tests and urine analysis will also be performed. After one year, patients who have low bone density (osteopenic and osteoporosis) determined from BMD measurements, will be treated with antiresorptive drugs. Biomarkers will be measured before and after this intervention and will be followed for one year. Breast cancer treatment induced bone loss can have tremendous negative effect on survivors' quality of life. Early identification of patients who are "fast bone losers" is essential. Early detection will allow an early intervention to prevent bone fracture. In addition, the ability to closely monitor the effects of intervention will allow adjustment of individual treatments as needed. Our method has the potential to be a clinically useful screening tool for breast cancer treatment management. This study will also offer researchers the opportunity to investigate the bone remodeling process directly. With an aging population, breast-cancer-treatment-induced bone loss can have a tremendous negative effect on breast cancer survivors and their quality of life [1-4]. Our objective is to develop a simple screening tool based on a urine test (41Ca assay) that can identify patients at very early stages of bone loss, as well as provide the means to monitor patients' responses to preventive drugs. These two pursuits will allow physicians to effectively treat high-risk patients early with preventive drugs, and monitor treatments' efficacy, which will improve patients' quality of life and reduce hospital costs.

描述（由申请人提供）：乳腺癌是女性最常见的癌症。随着乳腺癌幸存者数量的不断增加，癌症治疗引起的骨质流失和骨折正成为一个主要问题。芳香酶抑制剂 (AI) 作为雌激素阳性绝经后妇女的辅助治疗非常成功，可预防癌症进展。然而，由于雌激素严重耗尽，它也会增加骨质流失和骨折的可能性。早期识别骨丢失高风险患者、预防和频繁监测治疗干预对于降低骨折风险是绝对必要的。目前常用的骨密度（BMD）监测方法对骨密度的微小变化不敏感，也不适合频繁评估骨密度。我们提出了一种创新的测定方法来直接检测骨转换的早期变化，用于长期监测目的。我们假设尿液中的 41Ca/Ca 测量将提供 (a) 早期检测由于使用芳香酶抑制剂而导致的加速骨吸收，以及 (b) 由于抗吸收药物干预而动态监测骨形成过程。具体目标：确定长效 41Ca 的药代动力学 (PK) 的 AI 治疗反应，并与 BMD 测量、尿液 NTx 水平和血清 PINP 水平进行比较。使用 41Ca 测定法监测双膦酸盐干预对骨形成的影响，并将其与 BMD 测量值、尿液 NTx 水平和血清 PINP 水平进行比较。所有同意的绝经后乳腺癌患者将静脉注射微剂量的 41Ca。将在有或没有 AI 干预的情况下对尿液 41Ca 测定进行表征，以确定绝经后乳腺癌患者骨吸收的增强情况。该测定将进一步与 DXA 扫描、尿液 NTx 水平、血清 PINP 水平进行比较。还将进行 PTH、完整的血液代谢测试和尿液分析。一年后，根据 BMD 测量确定骨密度低（骨质减少和骨质疏松）的患者将接受抗骨吸收药物治疗。将在干预前后测量生物标志物，并跟踪一年。乳腺癌治疗引起的骨质流失会对幸存者的生活质量产生巨大的负面影响。及早识别“快速骨质流失者”患者至关重要。早期发现将有助于早期干预以防止骨折。此外，密切监测干预效果的能力将允许根据需要调整个体治疗。我们的方法有可能成为临床上有用的乳腺癌治疗管理筛查工具。这项研究还将为研究人员提供直接研究骨重塑过程的机会。随着人口老龄化，乳腺癌治疗引起的骨质流失会对乳腺癌幸存者及其生活质量产生巨大的负面影响[1-4]。我们的目标是开发一种基于尿液测试（41Ca 测定）的简单筛查工具，该工具可以识别处于骨质流失极早期阶段的患者，并提供监测患者对预防药物反应的方法。这两项追求将使医生能够尽早使用预防药物有效治疗高危患者，并监测治疗效果，从而改善患者的生活质量并降低医院费用。