# Body composition and breast cancer survival: immune and metabolic biomarkers in breast tumors

> **NIH NIH R01** · KAISER FOUNDATION RESEARCH INSTITUTE · 2020 · $699,075

## Abstract

ABSTRACT
There is growing evidence that breast cancer patients with adverse body composition (low muscle mass and
excess adiposity) have worse therapeutic responses and an increased risk of recurrence and death. Both low
muscle mass and excess adiposity promote systemic metabolic abnormalities like the metabolic syndrome.
While the impact of adverse body composition on the local tumor microenvironment remains unclear, data from
pre-clinical animal models and in vitro analyses suggest that adverse body composition could contribute to
impaired anti-tumor immunity and alterations in metabolic and proliferative signaling pathways. However, these
relationships have not been comprehensively studied in human breast cancer patients or within molecular
subtypes of breast cancer that have differing biology and prognosis. Developing and personalizing breast
cancer therapies will require understanding how systemic factors such as patient body composition and the
metabolic syndrome impact the local breast tumor microenvironment and therefore breast cancer survival. To
address this gap in knowledge, we propose a molecular epidemiologic study to determine if lower muscle
mass, excess adiposity and the metabolic syndrome impair the anti-tumor immune response by promoting T-
cell exhaustion (Aim 1) and/or by altering the activity of PI3K/AKT/mTOR pathways and proliferative signaling
(Aim 2) in the breast tumor microenvironment. We will further determine if alterations in these immune,
metabolic and proliferative signaling pathways mediate the association of adverse body composition with
breast cancer recurrence and breast cancer-specific mortality (Aim 3). To accomplish this, we will measure
gene expression levels in 1,400 archived clinical breast tumor samples selected from a unique cohort: more
than 4,000 stage II and III breast cancer patients with longitudinal follow-up and precise measures of muscle,
subcutaneous, and visceral adipose tissue. All these patients also have rich electronic medical record data on
cancer treatments and the metabolic syndrome. Since our sampling approach ensures representation across
each of four major clinicopathological categories defined by hormone receptor and human epidermal growth
factor receptor 2 status, we will be able to examine associations overall, and separately within each breast
cancer subtype. Using this premier data resource, we will examine how differences in the breast tumor
microenvironment caused by adverse body composition and the metabolic syndrome may mediate differences
in long-term breast cancer outcomes. The proposed study will help personalize existing breast cancer
therapies and develop future intervention approaches that consider both the molecular features of the tumor
and patient body composition. Furthermore, this study will identify tumor biomarkers that are appropriate
targets to be measured in future trials to improve body composition and the metabolic syndrome through
pharmacologic or lifestyle...

## Key facts

- **NIH application ID:** 10029647
- **Project number:** 1R01CA251589-01
- **Recipient organization:** KAISER FOUNDATION RESEARCH INSTITUTE
- **Principal Investigator:** Elizabeth Marjorie Cespedes Feliciano
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $699,075
- **Award type:** 1
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10029647

## Citation

> US National Institutes of Health, RePORTER application 10029647, Body composition and breast cancer survival: immune and metabolic biomarkers in breast tumors (1R01CA251589-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10029647. Licensed CC0.

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