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

• 批准号: 7490068
• 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
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7490068
• 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 Intervention; Early identification; Effectiveness of Interventions; 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; Numbers; Osteogenesis; Osteoporosis; Patient Monitoring; Patients; Pharmaceutical Preparations; Physicians; Population; Postmenopause; Prevention; Preventive; Principal Investigator; Process; Purpose; 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; improved; in vivo; innovation; malignant breast neoplasm; novel; prevent; programs; research study; response; tool; tumor progression; urinary

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。随着越来越多的乳腺癌幸存者，癌症治疗引起的骨丢失和骨折正在成为一个主要问题。芳香化酶抑制剂（AI）作为雌激素阳性绝经后妇女预防癌症进展的辅助治疗非常成功。然而，由于雌激素的严重消耗，它也会增加骨质流失和骨折的易感性。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。目前常用的监测骨矿物质密度（BMD）的方法对骨密度的微小变化既不敏感，也不适合频繁评估骨密度。我们提出了一种创新的检测方法，直接检测骨转换的早期变化，用于长期监测目的。我们假设尿中41 Ca/Ca的测量将提供（a）芳香化酶抑制剂使用导致的骨吸收加速的早期检测，和（B）抗吸收药物干预导致的骨形成过程的动态监测。 具体目的：确定AI治疗对长寿命41 Ca药代动力学（PK）的反应，并与BMD测量、尿NTx水平和血清PINP水平进行比较。 使用41 Ca测定监测双膦酸盐干预对骨形成的影响，并将其与BMD测量、尿NTx水平和血清PINP水平进行比较。 将对所有知情同意的绝经后乳腺癌患者静脉注射微量41 Ca。尿41 Ca测定将在有和没有AI干预的情况下进行表征，以确定绝经后乳腺癌患者骨吸收的增强。该测定将进一步与DXA扫描、尿NTx水平、血清PINP水平进行比较。还将进行PTH、全血代谢检查和尿液分析。一年后，通过BMD测量确定骨密度低（骨质减少和骨质疏松）的患者将接受抗吸收药物治疗。将在干预前后测量生物标志物，并随访一年。 乳腺癌治疗引起的骨丢失可能对幸存者的生活质量产生巨大的负面影响。早期识别“快速骨丢失者”的患者至关重要。早期发现将允许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乳腺癌治疗管理的临床有用的筛查工具。这项研究也将为研究人员提供直接研究骨重建过程的机会。随着人口老龄化，乳腺癌治疗引起的骨质流失可能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检测（41 Ca测定）的简单筛查工具，可以在骨丢失的早期阶段识别患者，并提供监测患者对预防药物反应的方法。这两个目标将使医生能够有效地治疗高危患者早期预防药物，并监测治疗的疗效，这将提高患者的生活质量，降低医院成本。