African-American women are disproportionately affected by triple negative breast cancer (TNBC), a form of breast cancer that does not express the three widely used biomarkers and therapeutic targets, namely Her-2, estrogen receptor and progesterone receptor. Consequently, these women do not benefit from the novel therapies (eg., Herceptin therapy) targeting the three biomarkers. TNBC are very aggressive, resulting in higher mortality rate in African-American women than women in other population. While TNBC is initially sensitive to chemotherapy, these women develop chemoresistance with no alternative treatment regimen available. Thus, there is a critical need to identify novel biomarkers for TNBC and develop specific therapeutic strategies to combat this health disparity. In preliminary studies, we have identified annexin A2 as a putative biomarker for TNBC. When Her-2 is negative, we find annexin A2 expression to be significantly increased, and conversely when Her-2 is overexpressed, annexin A2 expression is decreased. We hypothesize that AnxA2 overexpression accounts for the disproportionate occurrence of TNBC in African American women, and that AnxA2 is a useful biomarker and therapeutic target for TNBC. We will test this hypothesis through the following specific aims: 1) To integrate TNBC as a focus of education in an ongoing primary prevention program targeting high nsk AA women, 2) To establish the correlation of AnxA2 expression with poor pathological, prognostic variables and ethnicity in TNBC patients, and validate AnxA2 as a diagnostic biomarker for TNBC patients. 3) To delineate AnxA2-EGFR mediated downstream signaling pathway which regulates cancer cell proliferation, migration and invasion in TNBC, and 4) To establish AnxA2 as a therapeutic target in triple negative breast cancer. Our expectation is that successful completion of the proposed work will identify a specific biomarker for TNBC that could be targeted by novel therapeutic strategies. The proposed investigations will help in understanding the role of AnxA2 expression in the incidence of TNBC in various ethnic groups.

Public Health Relevance

Triple negative breast cancer, disproportionately affect Afncan-American women and is a significant health disparity problem. Our research is aimed at identifying novel biomarkers and devising therapeutic strategies to solve this public health problem.

Agency
National Institute of Health (NIH)
Institute
National Institute on Minority Health and Health Disparities (NIMHD)
Type
Exploratory Grants (P20)
Project #
5P20MD006882-03
Application #
8701898
Study Section
Special Emphasis Panel (ZMD1-RN)
Project Start
Project End
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
3
Fiscal Year
2014
Total Cost
$177,934
Indirect Cost
$53,762
Name
University of North Texas
Department
Type
DUNS #
110091808
City
Fort Worth
State
TX
Country
United States
Zip Code
76107
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Gibbs, Lee D; Chaudhary, Pankaj; Mansheim, Kelsey et al. (2018) ANXA2 expression in African American triple-negative breast cancer patients. Breast Cancer Res Treat :
Gibbs, Lee D; Vishwanatha, Jamboor K (2018) Prognostic impact of AnxA1 and AnxA2 gene expression in triple-negative breast cancer. Oncotarget 9:2697-2704
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