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Novel dietary interventions for reducing obesity-associated breast cancer

减少肥胖相关乳腺癌的新型饮食干预措施

基本信息

批准号：
10544502
负责人：
VICTORIA A CATENACCI
金额：
$ 61.66万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-01-01 至 2026-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10544502
关键词：
Acceleration Adherence Adipocytes Adult Adverse effects Affect Age Antiestrogen Therapy Attention Attenuated Behavior Therapy Behavioral Biological Biological Markers Body Weight decreased Breast Cancer Patient Breast Cancer Prevention Breast Cancer Risk Factor Breast Cancer survivor Caloric Restriction Cancer Control Cells Cessation of life Characteristics Clinical Clinical Research Data Development Dietary Intervention Disease Disease susceptibility Estrogen receptor positive Estrogens Extracellular Matrix Face Fibroblasts Foundations Future Growth Health Health Benefit Human Immune Incidence Individual Inflammatory Intermittent fasting Intervention Intervention Studies Intervention Trial Lead Life Style Malignant Neoplasms Mammary Neoplasms Mediator Medical Oncology Menopausal Status Metabolic Metabolic Diseases Metabolic dysfunction Modality Modeling Neoplasm Metastasis Newly Diagnosed Obesity Outcome Overweight Patient-Focused Outcomes Patient-derived xenograft models of breast cancer Patients Persons Phase Play Postmenopause Predisposition Premenopause Prognosis Protein Secretion Quality of life Randomized Research Personnel Resistance development Risk Role Science Specific qualifier value Stromal Cells Structure Thinness Time Time-restricted feeding Translating Tumor Promotion Tumor Subtype Weight Woman Work breast cancer diagnosis breast cancer progression cancer risk cancer subtypes circulating biomarkers clinically relevant common treatment dietary efficacy trial epidemiology study hormone therapy improved improved outcome innovation interdisciplinary collaboration intervention delivery intervention refinement malignant breast neoplasm mammary novel novel therapeutic intervention nutrition obesity treatment patient derived xenograft model patient population preclinical study therapy outcome triple-negative invasive breast carcinoma tumor tumor microenvironment tumor progression weight loss intervention

项目摘要

PROJECT SUMMARY Despite new treatment modalities, the incidence of breast cancer has remained steady in recent years with >250,000 new diagnoses and >40,000 deaths annually in the US. Concurrently, the proportion of US women with overweight or obesity continues to rise, and is approaching 70%. Obesity and metabolic disease (which occurs in lean and obese women) increase breast cancer incidence and worsen patient outcomes in women of all ages. Premenopausal women with obesity are at increased risk of triple negative (TN) breast cancer (lacking any targetable factors). Postmenopausal women with obesity incur more estrogen receptor (ER) positive breast cancer and are more likely to develop resistance to endocrine therapies. While estrogen is clearly an important part of this relationship, two key observations suggest that there may be estrogen-independent mechanisms at play: 1) obesity is accompanied by worse prognosis for estrogen-independent triple negative breast cancer; and 2) anti-estrogen therapies are less effective against ER+ breast tumors in women with obesity. Regardless of tumor subtype and menopausal status, excess weight is associated with poor outcomes for breast cancer patients. Weight loss is known to improve breast cancer outcomes, but most people cannot sustain the standard dietary weight loss strategies and weight regain is common. Intermittent energy restriction (IER) is a novel dietary weight loss strategy that may have more beneficial effects on metabolic health and on breast cancer risk and tumor progression. The work in this proposal will employ preclinical, clinical, and interventional studies, to examine a novel mechanism of obesity-associated tumor progression and the value and feasibility of innovative dietary interventions for eliminating obesity’s adverse effects on breast cancer. We have merged expertise in nutrition, obesity, and medical oncology to: 1) examine a novel role that cancer- associated fibroblasts (CAFs) and the tumor microenvironment (TME) may be playing in obesity-associated tumor progression; 2) investigate if the novel dietary weight loss strategy of IER can eliminate obesity-associated tumor progression; and 3) perform an ORBIT Phase IIa proof-of-concept study examining the ability of an IER- based weight loss intervention to reach meaningful clinical milestones in breast cancer patients afflicted with overweight and obesity and refine the intervention for delivery in a future randomized efficacy trial. If the objectives of this proposal are achieved, we will have: * Advanced our understanding of the obesity – breast cancer relationship, with evidence of a novel role for CAFs and the TME in obesity-associated tumor promotion for TN and ER+ breast cancer; * Established the foundation for IER weight loss trials in breast cancer survivors, with data that will help us adapt these strategies to the unique characteristics and needs of this patient population; and * Identified novel circulating biomarkers of a pro-metastatic TME, which may help identify patients most susceptible to metastatic disease.

项目总结