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

基本信息

批准号：
8688963
负责人：
Marilyn L Kwan
金额：
$ 61.56万
依托单位：
KAISER FOUNDATION RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
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/8688963
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

项目摘要

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（由申请人提供）：芳香酶抑制剂（AIS）已迅速替换了他莫昔芬（TAM）作为一线辅助荷尔蒙治疗或绝经后女性诊断为激素受体（HR） - 阳性阳性，早期的雌激素消耗。同源性触发的绝经后妇女骨折的骨折。到目前）医疗计划，从2006年至2013年开始，并随后到2016年。建立AIS的途径，将TAM替换为绝经后的荷尔蒙，通过利用丰富的流行病学，临床和药房，并与高素质生物镜联系在一起。。结果）与1）可修改的生活方式，例如身体表演，维生素D和钙盘使用，吸烟和酒精构造；，OPG，IL1，IL6，TNF¿，CSF）和25-羟基维生素D.将根据生活方式因素，遗传变化和血清生物标志物开发治疗，并与估计有230,000例新诊断的病例的模型进行比较。与健康的骨骼疗法相比，在术后健康疗法中，据估计，在术后，我们在途径研究中估计了13,000个裂缝Perhas Perhas。乳腺癌生存研究的一个重要差距，并减少在现实世界中临床环境中AI诱导的骨质疏松性骨折的负担。