Abstract P2-10-08: Racial disparities in breast cancer: Identifying predisposing clinical and molecular features associated with African American patients

Abstract

Abstract Background: Breast cancer (BC) mortality is higher in African-American women (AA) than in Caucasian women (CA). AA are also diagnosed at a younger age, have more aggressive subtypes and greater incidence of metabolic dysfunction such as obesity and diabetes. These disparities have been attributed to a confluence of socioeconomic, genetic and epigenetic factors. However, the distinctive tumor biology of AA BC is not yet fully elucidated, as AA remain underrepresented in breast cancer studies and databases. Here, we compared clinical and molecular BC features of AA and CA patients for insights into mechanisms associated with these racial disparities. Methods: The FLEX Registry Trial (NCT03053193) is a prospective study evaluating tissue collected from patients with stage I-III BC who have consented to receive MammaPrint(MP)/BluePrint(BP) and clinically annotated full genome (FG) data. FLEX subset analyses investigate new gene associations that may be relevant to BC biology. This sub-study includes 160 AA and 199 CA patients (n=359) enrolled since April 2017. Clinical characteristics used in the analysis include menopausal status, metabolic factors, stage, grade and IHC results. A comprehensive publication search (PubMed) was conducted to validate candidate genes involved in BC in AA, BC genes associated with epigenetic regulation and genes associated with metabolic syndrome. Hierarchical clustering was performed on FG microarray (Agilent) intensity data focusing on the candidate genes (50 probes targeting 37 unique genes). Gene expression was compared between race and MP/BP risk groups. Results: AA were predominately MP High Risk (HR) 67.5%, BP Luminal B 40.2%, BP Basal 22.6%. Interestingly, 40.0% of AA BP Basal were classified by IHC as ER+. CA were MP Low Risk (LR) 54.8%, BP Luminal A 54.8%. Clinically, there were no differences in histology, tumor size, nodal or menopausal status between AA and CA patients. AA had higher grade tumors, higher rates of type 2 diabetes and obesity. Three comparisons were performed: 1) AA and CA, irrespective of MP result, 2) AA and CA HR MP only, and 3) AA only, irrespective of MP result. In comparison 1) 15 unique genes showed significant differences (p<0.05) in gene intensities between AA and CA patients. A heatmap showed four major clusters; cluster 1 included mainly (72.3%) AA patients, and these were predominantly MP HR and BP Basal. In comparison 2) 9 unique genes had significant differences (p<0.05) in gene intensities, 6 of which were common to the first comparison. This showed three major clusters and a significant cluster among AA patients. Finally, comparison 3) found 20 unique genes with significant differences (p<0.05) in gene intensities, 10 of which were common to the previous comparisons. This showed two major clusters with one significant cluster among AA MP HR, BP Basal patients. In total, 11 unique genes showed significant differences in intensities in AA or AA with HR MP including CYP4F8, TWIST1/2, CCND2, FOXA1 and GSTP1. These genes have known functions regulating metabolism and cell cycle. Conclusions: Here we show AA patients were enriched for genes associated with metabolic syndrome and epigenetic regulation of metabolic syndrome. The aberrant function of these genes has been implicated in tumorigenesis, dysregulation of metabolism and drug resistance. Further validation is warranted to fully understand the association of these genes with the unique biology of breast cancer in AA. Citation Format: Raquel Nunes, Lisa E. Blumencranz, Heather M Kling, Sahra Uygun, Sarah Untch, Erin B Yoder, Jennifer A Crozier, William Audeh. Racial disparities in breast cancer: Identifying predisposing clinical and molecular features associated with African American patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-10-08.