Lifestyle and Molecular Factors of Bone Health in Breast Cancer Survivors

乳腺癌幸存者的生活方式和骨骼健康的分子因素

• 批准号: 8539751
• 负责人: Marilyn L Kwan
• 金额: $ 50.01万
• 依托单位: KAISER FOUNDATION RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-04 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8539751
• 关键词: 25-hydroxyvitamin D; Address; Adjuvant; Age; Alcohol consumption; Aromatase Inhibitors; Biological Assay; Biological Markers; Bone Density; Bone Resorption; Calcium; California; Cancer Patient; Cancer Prognosis; Cancer Survivor; Cancer Survivorship; Caring; Clinical; Clinical Trials; Cohort Studies; Coupled; Data; Diagnosis; Diet; Direct Costs; Early treatment; Enrollment; Environment; Epidemiology; Estrogen Metabolism; Estrogens; Facilities and Administrative Costs; Fracture; Future; General Population; Genes; Genetic Variation; Genotype; Guidelines; Health; Health Care Costs; High Risk Woman; Hip Fractures; Hormonal; Hormone Receptor; IL6 gene; Interleukin-1; Knowledge; Life; Life Style; Link; Managed Care; Medical; Modeling; Molecular; Molecular Genetics; Newly Diagnosed; Osteogenesis; Osteoporosis; Outcome; Pathway interactions; Patients; Performance; Pharmacy facility; Physical activity; Population; Positioning Attribute; Postmenopause; Predictive Value; Prevention; Prospective Studies; Public Health; Quality of life; Relative (related person); Request for Applications; Research; Risk; Risk Assessment; Risk Factors; Serum; Smoking; Spinal Fractures; Staging; Survivors; TNF gene; TNFSF11 gene; Tamoxifen; Time; Validation; Vitamin D; Woman; base; bone; bone health; bone metabolism; care systems; clinical risk; clinically significant; cytokine; design; disability; genome-wide; high risk; hormone therapy; improved; lifestyle factors; malignant breast neoplasm; mortality; osteoporosis with pathological fracture; primary outcome; programs; prospective; public health relevance; screening; secondary outcome; skeletal; tool

DESCRIPTION (provided by applicant): Aromatase inhibitors (AIs) have been rapidly replacing tamoxifen (TAM) as first-line adjuvant hormonal therapy for postmenopausal women diagnosed with hormone receptor (HR)-positive, early-stage breast cancer. The profound estrogen depletion triggered by AIs is responsible for improved outcomes compared to TAM, yet AI therapy can negatively impact bone health, elevating the already high risk of fractures in postmenopausal women. Osteoporotic fractures at older age can result in markedly increased mortality, poor quality of life, and staggering healthcare costs. Despite these outcomes, risk factors for fracture specific to postmenopausal breast cancer patients taking AIs remain surprisingly understudied. To date, no validated tools exist for fracture risk assessment specific to postmenopausal women prior to initiation of AI therapy. This application requests to conduct for the first time a prospective study on bone health in 2,062 postmenopausal breast cancer patients who received AI therapy in the Pathways Study, a prospective cohort study of breast cancer prognosis in the Kaiser Permanente Northern California (KPNC) Medical Care Program, enrolled from 2006-2013 and followed through 2016. The establishment of Pathways was concurrent with AIs widely replacing TAM as hormonal therapy for postmenopausal patients. By leveraging a rich body of epidemiologic, clinical and pharmacy data linked with high-quality biospecimens in Pathways, we have a unique opportunity to conduct one of the first in-depth studies of AI-associated fractures in breast cancer patients. Among postmenopausal women who received AI therapy for early-stage, HR-positive breast cancer, we will investigate the risk of fractures (primary outcome) and osteoporosis (secondary outcome) in association with 1) modifiable lifestyle factors such as physical activity, diet, vitamin D and calcium supplement use, smoking, and alcohol consumption; 2) germline genetic variations in estrogen and bone metabolism pathways with validation of findings using genome-wide assays; and 3) the associations of serum biomarkers, including BAP for bone formation and TRAP5b for resorption, six key regulatory cytokines (RANKL, OPG, IL1, IL6, TNF¿, CSF), and 25-hydroxyvitamin D. Finally, a prediction model for fracture risk in postmenopausal breast cancer patients on AI therapy will be developed based upon lifestyle factors, genetic variations, and serum biomarkers and compared with models intended for the general healthy population. Over 2.5 million women with breast cancer live in the U.S. today, with an estimated 230,000 newly diagnosed cases in 2011. An excess of 13,000 fractures per year has been estimated among postmenopausal survivors compared to their healthy counterparts. Therefore, understanding the health effects of AI therapy on risk of skeletal outcomes is of great public health importance. In the Pathways Study, we now have an exceptional opportunity to address an important gap in breast cancer survivorship research, and to reduce the burden of AI-induced osteoporotic fractures in a real-world clinical setting.

描述(申请人提供)：芳香酶抑制剂(AIs)已迅速取代他莫昔芬()，成为激素受体(HR)阳性的早期乳腺癌绝经后妇女的一线激素辅助疗法。与相比，人工智能引发的严重雌激素枯竭是预后改善的原因，但人工智能治疗可能会对骨骼健康产生负面影响，增加绝经后女性本已很高的骨折风险。老年骨质疏松性骨折会导致死亡率显著增加，生活质量下降，以及惊人的医疗费用。尽管有这些结果，但令人惊讶的是，接受人工授精治疗的绝经后乳腺癌患者发生骨折的危险因素仍未得到充分研究。到目前为止，还没有有效的工具用于在开始人工智能治疗之前对绝经后妇女进行骨折风险评估。这项申请要求首次在路径研究中对2,062名接受人工智能治疗的绝经后乳腺癌患者进行骨骼健康前瞻性研究，路径研究是一项关于乳腺癌预后的前瞻性队列研究，在北加州凯撒永久医疗计划(KPNC)中进行，从2006年到2013年登记，并一直跟踪到2016年。Path的建立与AIS广泛取代作为绝经后患者的激素治疗是同步的。通过利用丰富的流行病学、临床和药学数据与高质量的生物显微镜在路径中的联系，我们有一个独特的机会对乳腺癌患者的人工智能相关骨折进行首批深入研究之一。在接受人工智能治疗的早期HR阳性乳腺癌的绝经后妇女中，我们将调查骨折(主要结果)和骨质疏松症(次要结果)的风险与1)可改变的生活方式因素，如体力活动、饮食、维生素D和补钙剂的使用， 最后，将根据生活方式因素、遗传变异和血清生物标记物，建立绝经后乳腺癌患者骨折风险的预测模型，并与面向普通健康人群的模型进行比较。今天，美国有超过250万乳腺癌患者，2011年估计有23万新诊断病例。据估计，与健康的女性相比，绝经后的幸存者每年有超过13,000例骨折。因此，了解人工智能治疗对骨骼结局风险的健康影响具有重要的公共卫生意义。在Path研究中，我们现在有一个特殊的机会来解决乳腺癌存活率研究中的一个重要缺口，并在现实世界的临床环境中减轻人工智能导致的骨质疏松性骨折的负担。