# Impact of race and ethnicity on outcomes in patients with hormone receptor-positive breast cancer treated with CDK4/6 inhibitors

> **NIH NIH P20** · TEXAS SOUTHERN UNIVERSITY · 2024 · $36,171

## Abstract

Breast cancer (BC) is the most common cancer in women worldwide and is the second leading cause of cancer
death in women. However, the advances in outcomes of BC patients have been limited to a subset of the affected
population, namely European American (EA) women compared to their African American (AA) women
counterparts. Despite various hormone therapies, the hormone receptor (ER/PR) positive (HR+), human
epidermal growth factor receptor 2 (HER2)-negative (HR+/Her2-) subtype of BC remains difficult to treat. Cyclin-
dependent kinase 4 and 6 inhibitors (CDK4/6i) have recently emerged as a new treatment strategy.
Interestingly
a 2022 population-based study confirmed that while the outcomes for HR+/Her2- metastatic BC have improved
since CDK4/6i were introduced in 2015, this effect is primarily driven by the improved overall survival (OS) in
non-Hispanic EA
patients, without significant improvement in AA or Hispanics patients.
The relative contribution
of genetic factors vs. medication adherence or social determinants of health (SDOH) on such outcomes is less
understood. Recent efforts to address this gap include databases such as ‘All of Us’, designed to better
understand the interplay between genetic factors and social determinants. From a functional point, our
preliminary analysis of
The Cancer Genomic Atlas (TCGA) data shows decreased mRNA expression of FAT1,
FAT4 and RB1, the major genes involved in resistance to CDK4/6i, in AA compared to EA HR+/Her2- BC.
Thus,
this project will do preliminary analysis of two aspects of BC therapy resistance in AA BC patients. Aim-1 of this
project will assess the impact of medication adherence and various social determinants on clinical outcomes of
female BC patients treated with CDK4/6i. Aim-2 will analyze the impact of genetic variations and low expression
of FAT1, FAT4 and RB1 genes on the development of resistance to CDK4/6i in AA women with BC. We will use
surveys, verbal medication review and EHR documentation of medication possession to gather information
related to medication adherence and social determinants that may impact compliance. We will also analyze the
prevalence of germline and somatic variations and epigenetic status of FAT1, FAT4 and RB1 genes in BC
patients of EA and non-EA ancestry. Using computational modeling, we will predict the functional networking of
FAT1, FAT4 and RB1 low expression in AA BC patients. Using established databases, clinical information
obtained from the electronic health record (EHR), and surveys exploring SDOH and medication adherence
patterns, this pilot aims to generate preliminary data exploring the impact of these factors on treatment outcomes
in AA vs. EA patients receiving oral targeted therapy, including CDK4/6i. Discovery of AA-centric genetic
variations and the impact of low expressed FAT1, FAT4 and RB1 genes in the functional networking will be
critical in pre-selecting AA BC patients that may benefit from CDK4/6i therapy.

## Key facts

- **NIH application ID:** 10932910
- **Project number:** 5P20CA284967-02
- **Recipient organization:** TEXAS SOUTHERN UNIVERSITY
- **Principal Investigator:** Rodney Hunter
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $36,171
- **Award type:** 5
- **Project period:** 2023-09-21 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10932910

## Citation

> US National Institutes of Health, RePORTER application 10932910, Impact of race and ethnicity on outcomes in patients with hormone receptor-positive breast cancer treated with CDK4/6 inhibitors (5P20CA284967-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10932910. Licensed CC0.

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