R01CA258766

Novel Dietary Interventions for Reducing Obesity-Associated Breast Cancer - Project Summary

Despite new treatment modalities, the incidence of breast cancer has remained steady in recent years with over 250,000 new diagnoses and over 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 occur in both lean and obese women, increase breast cancer incidence and worsen patient outcomes in women of all ages.

Premenopausal women with obesity are at an increased risk of triple negative (TN) breast cancer, which lacks any targetable factors. Postmenopausal women with obesity are more likely to develop estrogen receptor (ER) positive breast cancer and are also 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. Firstly, obesity is accompanied by worse prognosis for estrogen-independent triple negative breast cancer. Secondly, 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.
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.
- Identified novel circulating biomarkers of a pro-metastatic TME, which may help identify patients most susceptible to metastatic disease.

The Regents Of The University Of Colorado

TO IDENTIFY CANCER RISKS AND RISK REDUCTION STRATEGIES, TO IDENTIFY FACTORS THAT CAUSE CANCER IN HUMANS, AND TO DISCOVER AND DEVELOP MECHANISMS FOR CANCER PREVENTION AND PREVENTIVE INTERVENTIONS IN HUMANS. RESEARCH PROGRAMS INCLUDE: (1) CHEMICAL, PHYSICAL AND MOLECULAR CARCINOGENESIS; (2) SCREENING, EARLY DETECTION AND RISK ASSESSMENT, INCLUDING BIOMARKER DISCOVERY, DEVELOPMENT AND VALIDATION; (3) EPIDEMIOLOGY; (4) NUTRITION AND BIOACTIVE FOOD COMPONENTS; (5) IMMUNOLOGY AND VACCINES; (6) FIELD STUDIES AND STATISTICS; (7) CANCER CHEMOPREVENTION AND INTERCEPTION; (8) PRE-CLINICAL AND CLINICAL AGENT DEVELOPMENT; (9) ORGAN SITE STUDIES AND CLINICAL TRIALS; (10) HEALTH-RELATED QUALITY OF LIFE AND PATIENT-CENTERED OUTCOMES; AND (11) SUPPORTIVE CARE AND MANAGEMENT OF SYMPTOMS AND TOXICITIES. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM; TO STIMULATE TECHNICAL INNOVATION; TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING; TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT; AND TO FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY WOMEN AND SOCIALLY/ECONOMICALLY DISADVANTAGED PERSONS.SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS; TO FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS; TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING, AND FOSTER PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY WOMEN AND SOCIALLY/ECONOMICALLY DISADVANTAGED PERSONS.

93.393 - Cancer Cause and Prevention Research

National Cancer Institute (NCI) [HHS - NIH]

Aurora, Colorado 80045 United States

Single Zip Code

Cancer Prevention and Control Clinical Trials Grant Program (R01 Clinical Trial Required) (PAR-21-035)

Amendment Since initial award the total obligations have increased 414% from $606,900 to $3,121,862.