# Novel dietary interventions for reducing obesity-associated breast cancer

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2022 · $606,900

## Abstract

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...

## Key facts

- **NIH application ID:** 10367368
- **Project number:** 1R01CA258766-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** VICTORIA A CATENACCI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $606,900
- **Award type:** 1
- **Project period:** 2022-01-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10367368

## Citation

> US National Institutes of Health, RePORTER application 10367368, Novel dietary interventions for reducing obesity-associated breast cancer (1R01CA258766-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10367368. Licensed CC0.

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