# Project 1:The Carolina Breast Cancer Study

> **NIH NIH P50** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $585,719

## Abstract

Project 1 Abstract
Black women suffer higher incidence of poor-prognosis breast cancer subtypes and worse stage-specific
mortality. Our previous Carolina Breast Cancer Study(CBCS)-based SPORE discoveries have integrated
population-based epidemiology with tumor biology to demonstrate that young black women are more likely to
develop Basal-like tumors. More recently, we found that black women also have higher frequency of Luminal B
and HER2-enriched breast tumors. Furthermore, even among the best-prognosis clinical subset of estrogen
receptor (ER)-positive/HER2-negative cancers, black women have higher risk of recurrence (ROR) scores.
These findings implicate tumor biology as a key contributor to racial mortality disparities. Some tumor factors
(i.e., higher frequency of HER2-enriched subtype) may be targetable, illustrating how population-based
genomics can advance precision medicine. In this Project, we propose to deepen our understanding of racial
differences in tumor biology, etiology and progression, with a focus on tumor mutational signatures and
immune responses. The frequency of specific mutations (i.e. TP53, PIK3CA), and the overall patterns of
somatic mutations (mutational signatures) can be informative about the underlying biological processes that
have gone awry from the earliest stages of carcinogenesis. In addition, new discoveries have emphasized the
importance of the immune system in breast cancer etiology and progression. With our rich resource of tumor
biospecimens (exceptional 96% tumor procurement from 3000 cases), we will sequence tumor DNA and
identify mutational signatures in black and white women (Aim 1) and we will characterize tumor immune
microenvironments using six immunohistochemical markers and RNA profiling for 50 genes (Aim 2). While The
Cancer Genome Atlas (TCGA) has evaluated racial differences in tumors with hundreds of thousands of data
points per patient, limitations included small numbers of black participants (CBCS is ten-fold larger than
TCGA), a sampling scheme that was not population-based, and lack of detailed covariate and follow-up data.
TCGA advances have allowed us to increase sequencing efficiency for population-based work and have
helped in developing an efficient RNA panel for immune profiling, resulting in a plan for cost-effective collection
of mutational signatures and expression profiles in 2000 women (1000 black, 1000 white, sampling from the
entirety of CBCS). Utilizing these advances in the context of the CBCS, we hypothesize that mutational
signatures and immune responses are differentially associated with race, age, and breast cancer subtype. We
also expect to identify some mutational signatures that vary as a function of immune profiles. The tumor
biological variables collected in Aims 1 and 2 will be assessed as predictors of breast cancer recurrence and
survival. In addition, impact of tumor biology may be confounded by other patient-level factors such as
socioeconomic status, access to ...

## Key facts

- **NIH application ID:** 10244929
- **Project number:** 5P50CA058223-27
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Melissa A. Troester
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $585,719
- **Award type:** 5
- **Project period:** 1997-08-05 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10244929

## Citation

> US National Institutes of Health, RePORTER application 10244929, Project 1:The Carolina Breast Cancer Study (5P50CA058223-27). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10244929. Licensed CC0.

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