# Immune Microenvironments and Hepatocyte Growth Factor Signaling Interactions in Breast Cancer Disparities

> **NIH NIH U54** · NORTH CAROLINA CENTRAL UNIVERSITY · 2024 · $232,590

## Abstract

PROJECT SUMMARY / ABSTRACT – Project 1
Black women suffer disproportionately from higher mortality rates of breast cancers (BC) compared to White
women. A driving force in patient outcome is the type of cancer diagnosis and the available treatment options.
We focus on two highly aggressive BC subtypes: the hormone receptor negative basal-like breast cancer (BLBC)
and the under-studied and deadly inflammatory breast cancer (IBC). Black women present with higher rates of
BLBC vs. White women, and since highly effective therapies are lacking, survival is poor. The NCI states IBC is
more common and diagnosed in younger Black women, and is often hormone receptor negative. Clearly a need
to conduct more advanced studies into these lethal BCs, and their common themes, is critical for patient survival
and understanding disparate outcomes. Many studies assessing differences in BCs in Black women and White
women examine tumor characteristics; however, etiologic factors that lead to this disparity remain poorly defined.
Our data show Black women have unique immune and stromal cell infiltrate and altered protein levels within
normal breast and tumor microenvironments. Our objective is to identify mechanisms involved in the progression
of aggressive, metastatic BC in Black women as a consequence of stromal effects at the site of the cancerous
lesion. Aim 1 takes advantage of our published studies and pilot expression datasets detailing race and tumor-
subtype specific stromal interactions that identified a focused pathway, hepatocyte growth factor (HGF) signaling.
We propose to use groundbreaking tools to identify the cell-type specific source, levels, and spatial orientation
of our signaling pathway molecules within heterogeneous tumors. We will compare these complex data between
Black and White BLBC and IBC tumors. Next, we will measure the expression of an HGF functional
polymorphism, which is highly expressed in Black women. This genetic difference likely results in a significantly
poorer prognosis and survival rate. These data will define subsets of patients who may benefit the most from
HGF/MET therapeutics, as this has been a limiting clinical setback. Aim 2 will then evaluate novel immune
signature contributions to IBC pathogenesis, and test their association with HGF signaling, race, and poorer
outcomes. Aim 3 will use robust experimental studies focused on deregulated DNA repair machineries to
elucidate the mechanistic details of the HGF polymorph and its consequence of HGF over-expression. These
data will significantly contribute to overcoming our lack of understanding of this highly aggressive IBC and provide
a robust signature to identify those at risk for developing IBC. Our team has established research partnerships
that provide access to resources including the Carolina Breast Cancer Study: a unique epidemiologic study from
ethnically diverse patients. By studying BLBC that has distinct immune/wound healing signatures together with
the underst...

## Key facts

- **NIH application ID:** 10914323
- **Project number:** 5U54MD012392-08
- **Recipient organization:** NORTH CAROLINA CENTRAL UNIVERSITY
- **Principal Investigator:** Kevin Peter Williams
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $232,590
- **Award type:** 5
- **Project period:** 2017-09-20 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10914323

## Citation

> US National Institutes of Health, RePORTER application 10914323, Immune Microenvironments and Hepatocyte Growth Factor Signaling Interactions in Breast Cancer Disparities (5U54MD012392-08). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10914323. Licensed CC0.

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