# Impact of the Breast Cancer Immune Microenvironment on Racial Disparities and Survivorship

> **NIH NIH F31** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $37,102

## Abstract

PROJECT SUMMARY
Breast cancer (BC) is the most commonly diagnosed malignancy and second leading cause of cancer-related
deaths among women in the US. Among all BC cases, black women suffer higher incidence of poor-prognosis
BC subtypes and worse stage-specific mortality. Growing evidence supports the importance of the immune
component of the BC microenvironment (BCME) in clinical outcomes. However, despite an abundance of clinical
trials and retrospective studies investigating the immune microenvironment in BC, biomarkers of immune
response are lacking and there is limited research regarding differences by race. By studying immune cells and
immune-related gene expression alone, the positive prognostic utility of tumor infiltrating lymphocytes in BC thus
far has been limited to triple negative and HER2-positive subtypes. The identification of a tumor-cell specific
biomarkers associated with BC immunogenicity could help identify additional candidates for immunotherapy. In
this regard, TP53 mutations are the most frequently occurring mutation in BC, vary in frequency by race, and
are associated with immune response in several tumor types. However, literature addressing the association
between TP53 dysfunction and BC immunogenicity is conflicting, and has never been studied in the context of
racial disparities. Thus, whether and how immune response differs by race, p53 functional status and survival
represents a critical knowledge gap in BC. To address this gap, I will leverage two major BC cohorts rich in
molecular, histological, clinical and epidemiological data: 1) the Carolina Breast Cancer Study (CBCS), a large
population-based study designed to investigate racial disparities in BC, and 2) The Cancer Genome Atlas
(TCGA) BC cohort, a well-known study with multiple data platforms for each sample. Using these resources, I
have obtained preliminary data suggesting that gene expression related to adaptive immune response is
enriched in breast tumors from black women vs non-black women, and that dysfunction in the p53 pathway is
associated with this response. Based on these findings, I hypothesize that differences in the immune BCME
contribute to racial disparities and survivorship outcomes, and that p53 function is a tumor-intrinsic mediator of
this process. I will test my hypothesis with two specific aims. In aim 1, I will characterize immune BCME
phenotypes using RNA expression profiling and immunohistochemistry and will evaluate associations with race,
age, tumor intrinsic subtypes and survival. In aim 2, I will investigate the relationship between TP53 functional
status and immune phenotypes in association with race and tumor intrinsic subtype. Given the low representation
of black women in clinical trials and gene expression studies, this will be the largest study of its kind to investigate
the immune BCME in black and non-black women. The results of this work will collectively elucidate how the
immune BCME contributes to tumor progression leadi...

## Key facts

- **NIH application ID:** 10141571
- **Project number:** 1F31CA257388-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Alina Marie Hamilton
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $37,102
- **Award type:** 1
- **Project period:** 2021-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10141571

## Citation

> US National Institutes of Health, RePORTER application 10141571, Impact of the Breast Cancer Immune Microenvironment on Racial Disparities and Survivorship (1F31CA257388-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10141571. Licensed CC0.

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