# Palmitic Acid and Basal-like Breast Cancer Progression

> **NIH VA I01** · BALTIMORE VA MEDICAL CENTER · 2021 · —

## Abstract

Background/Rationale: It is estimated that approximately 316,000 women will be newly
diagnosed with breast cancer in the United States (U.S.) each year, and 40,000 women will
die of breast cancer this year alone. Basal-like breast cancer accounts for 15-20% of all
diagnosed breast cancer depending on patient population. These patients are commonly
known as triple negative breast cancer because most cases often lack expression of
estrogen receptor α (ER), progesterone receptor (PR), and human epidermal growth factor
receptor 2 (HER-2). The absence of PR, ERa, and HER-2 commonly found in basal-like
breast cancer leads to these patients unlikely to respond to hormone therapies or HER-2
targeted therapies. Thus, basal-like breast cancer is highly aggressive, and often results in
lung and brain metastasis. Understanding risk factors for basal-like breast cancer invasion
and metastasis is urgently needed for identification of novel and specific molecular targets.
Because women represent the fastest growing demographic in the US Veteran population,
breast cancer is an increasingly significant public health issue for the Veterans Health
Administration. Our proposed studies will investigate the transition from early-stage basal-like
breast cancer to invasive breast cancer.
Objectives: Palmitic acid is one of the predominant saturated fatty acids in the western diet.
The goal of this study is to determine how high-palmitic acid (HPA) intake acts as a risk
factor to facilitate basal-like breast cancer invasion. Based on our preliminary studies, we
hypothesize that HPA increases the endothelial lipase ( LIPG) activity, which is a key driver
of invasive progression in early-stage basal-like breast cancer. We also hypothesize that
HPA initiates defective myoepithelial cell differentiation or loss of the mature myoepithelium,
which allows tumor cell invasion.
Methods: Specific Aim 1 will examine how HPA converts quiescent LIPG-negative tumor
cells into LIPG-positive tumor-initiating cells for early-stage basal-like breast cancer invasion.
Specific Aim 2 will investigate how LIPG signaling pathways contribute to loss of normal
myoepithelial cell function in HPA conditions. We have initiated studies screening natural
compounds combined with computational drug discovery approaches, and identified a potent
LIPG inhibitor DDL-1. Specific Aim 3 will determine if inhibition of LIPG prevents early-stage
basal-like breast cancer to invasive breast cancer progression in HPA conditions. We have
developed a new nanoparticle-based drug delivery system to deliver DDL-1 into mammary
myoepithelial cells and tumor cells. We will use mouse models of early-stage basal-like breast
cancer to study the effect of DDL-1 administration on the incidence of invasive breast cancer
and circulating tumor cells in HPA conditions.
Results: By identifying a mechanism by which breast cancer invasion occurs, we are hopeful
that we can design a novel chemoprevention solution to inhibit tumor inva...

## Key facts

- **NIH application ID:** 10046276
- **Project number:** 5I01BX004264-03
- **Recipient organization:** BALTIMORE VA MEDICAL CENTER
- **Principal Investigator:** Qun Zhou
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-10-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10046276

## Citation

> US National Institutes of Health, RePORTER application 10046276, Palmitic Acid and Basal-like Breast Cancer Progression (5I01BX004264-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10046276. Licensed CC0.

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