Abstract B03: Racial Variation in Annexin A2 (AnxA2) Gene Expression and Poor Outcome in Triple-Negative Breast Cancer

Abstract

Abstract Background: Triple-negative breast cancer (TNBC) is identified by the absence of three major receptors (estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2)) that drive most breast cancers. The incidence of TNBC is associated with health disparity due to its disproportionate occurrence in African American (AA) women and its association with worst overall survival in AA women. Previously, our lab in breast cancer has investigated the prevalence, functionality, and mechanistic properties of one of the members of the human annexin family, Annexin A2 (AnxA2), a 36 kDa calcium-dependent phospholipid binding protein. Our previous studies and others have shown that AnxA2 is overexpressed in TNBC and has a reciprocal relationship with HER2 at mRNA and protein levels, but its association with racial variation and clinical outcomes is unknown. Methods: AnxA2 mRNA expression was evaluated in breast cancer subtypes from The Cancer Genome Atlas (TCGA) Breast Invasive Carcinoma (BRCA) mRNA database that includes 1,094 patients. Associations between clinical outcomes and AnxA2 gene expression were tested in a genome wide association study of combined publicly available microarray datasets that includes 4,147 patients (mean follow-up of 69 months). Two tissue microarrays (TMA) consisting of 154 breast cancer patient samples of various subtypes and forty archived paraffin-embedded breast tissues (TNBC and normal tissue) were collected from patients based on ethnicity and analyzed by immunohistochemistry and scored by a clinical pathologist in a blind study to provide scores (0,+1,+2,+3) based on AnxA2 staining intensity. Results: AnxA2 gene expression was significantly increased in TNBC in comparison to other breast cancer subtypes. Furthermore, AnxA2 gene expression was significantly elevated in AA (n=158) women in comparison with Caucasian (CA; n=654, P<0.0001) and Hispanic (HA; n=51, P<0.0001) women and was significantly associated with TNBC in AA women. High expression levels of AnxA2 were associated with reduced overall survival (hazard of death = 2.66; 95% confidence interval {CI] = 1.14 - 6.25, P = 0.0192), reduced relapse free survival (hazard of relapse = 1.45; 95% confidence interval {CI] = 1.12 - 1.89, P = 0.0051), and reduced distant metastasis free survival (hazard of metastasis = 1.7; 95% confidence interval {CI] = 1.00 - 2.91, P = 0.048) in TNBC (basal-like intrinsic subtype). AnxA2 gene expression was not associated with poor outcome in other intrinsic breast cancer subtypes, such as Luminal A, Luminal B, and Her-2, indicating the specific association of AnxA2 with the aggressive behavior of TNBC. Analysis of breast tumor subtypes and normal tissues confirmed that AnxA2 is highly expressed in TNBC compared to its low to negligible expression in other subtypes and normal tumors. Conclusion: AnxA2 overexpression is associated with racial variation and is a potential prognostic and diagnostic candidate for TNBC. Impact: AnxA2 has potential prognostic and diagnostic value, implicating a role for AnxA2 in the aggressive biology of TNBC in AA women. Citation Format: Lee D. Gibbs, Pankaj Chaudhary, Jamboor K. Vishwanatha. Racial Variation in Annexin A2 (AnxA2) Gene Expression and Poor Outcome in Triple-Negative Breast Cancer. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr B03.