The goal of our proposed project is to examine the role of rurality, and neighborhood disadvantage (ND) in racial disparities in breast cancer (BC) mortality between Black and White patients in Alabama, including its ‘Black Belt’ region, an ideal setting to study the impact of rural and urban residency and race on BC outcomes. ND comprises detrimental aspects of a neighborhood that influence health and will be measured using the area deprivation index (ADI); ADI is a composite measure of ND calculated using 17 US census indicators, including poverty, income, education, employment, and housing quality. This project will improve our understanding of how ND interacts with individual-level factors to drive racial disparities in BC outcomes by 1) evaluating the association between ND and BC mortality in Black and White patients in Alabama, as well as the effect of rural vs. urban residency on racial disparities in BC mortality; 2) developing an interpretable machine learning model that integrates neighborhood-level and individual-level data to predict BC mortality- which can inform community-level approaches to mitigate these disparities.

Breast-conserving surgery (BCS) is a procedure for early-stage breast cancer that removes the cancer while keeping most of the breast. A key challenge is ensuring all cancer cells are removed, known as achieving clear margins. Currently, specimen radiography (SR) is used during surgery to check this, but it’s not always reliable, often leading to additional surgeries. This project aims to improve margin assessment using artificial intelligence (AI). We will develop and validate AI tools that provide real-time, accurate assessments during surgery. First, we’ll create an automated system to prepare training data by analyzing pathology reports and segmenting images. We’ll start with 2,000 SR images and reports from UAB. Next, we’ll build an AI model using forward-forward contrastive learning (FFCL) technology to accurately classify SR image margins, addressing the challenge of differentiating similar-looking tissues. Our team brings together experts in medical imaging, natural language processing, breast imaging, and data security, making us well-equipped to tackle this challenge. This project can potentially improve surgical decision-making and patient outcomes.

Macrophages are normal cells in the body that when in tumors (tumor-associated macrophages, TAMs) they help drive tumor growth. We have found that the protein PU.1 controls TAM function, both as part of 1) the colony-stimulating factor 1 (CSF1) receptor/PU.1 signaling pathway and 2) PU.1’s regulation of genes by its interaction with highly active areas of the genetic sequence called superenhancers. In this award, we will target both of these ways PU.1 regulates TAM function using small molecule inhibitors and microparticle-mediated drug delivery systems in mouse models of primary breast cancer tumors across subtypes.

It is appreciated that the nerve growth into the tumor promotes breast cancer, and yet the underlying mechanisms remain obscure. This proposal investigates how this process is modulated by a type of cells from our immune system. Findings obtained here will open a new avenue of investigation in the field of breast cancer research, and formulate new therapeutic approaches to treat this most prevalent and fatal form of cancer in women.

Black women with breast cancer are at an increased risk of heart problems like high blood pressure, stroke, and premature death. The ECHO: Exploring Cardiovascular Health Outcomes in Black Breast Cancer Survivors study will provide insight on Black breast cancer survivor’s perceptions of heart health and health behaviors. With a community advisory board, we will work to co-create an intervention that can educate and support Black breast cancer survivors to achieve greater heart health.

Many breast cancer patients are suffering from malignant progression of the disease and its spread to other organs (metastasis). The arteriolar niche (microenvironment) due to the formation of new blood vascular networks (angiogenesis) may harbor a subpopulation of cancer stem-like cells, thus promoting progression and metastasis. Understanding fundamental mechanisms of this niche establishment in breast cancers will provide insight into the discovery of innovative and effective treatment strategies to benefit these patients with aggressive and lethal disease.

Because of the lack of targeted treatment, triple-negative breast cancer (TNBC) is challenging to treat effectively. To improve the outcome of TNBC, we need to have new treatment options that disable the mechanisms by which cancer cells survive cytotoxic chemotherapy. We will test a new approach to inhibit these survival mechanisms with the goal of killing the tumor cells and reducing metastasis.

Immune cells are an important component of the tumor mass and their
composition and spatial distribution can greatly influence disease progression
and therapeutic outcomes. African American women with or without a breast
cancer diagnosis exhibit higher levels of cortisol, a stress hormone, in their
blood than Caucasian American (CA) women, likely due to their greater
exposure to psychological and socioeconomic stressors. We will examine the
immune landscape of AA and CA breast tumors and associate it with serum
cortisol levels to suggest a biological basis for prominent racial disparities in
the clinical outcomes of these patients.

The goal of this project is to study the mechanism by which a novel AKT small molecule degrader inhibits breast cancer cell proliferation and division. In addition, we will explore the anti-tumor immune response triggered by AKT degrader treatment. Overall, we believe breast cancer patients with PI3K/AKT/PTEN pathway mutations will benefit from this novel therapeutic strategy.