Abstract 4246: Characterizing breast cancer health disparities through molecular and genomic profiling of a diverse breast cancer cohort

The major indicators of breast cancer health disparities may include higher incidence, earlier onset, faster progression, and poorer outcomes. The ultimate goal of health disparities research is to elucidate actionable mechanisms of these differences to define the means of intervention that will help reduce the disparity. Breast cancer is the most common cancer and second leading cause of cancer death in American women and the new cases of invasive cancer have been increased lately in the United State. It is a heterogeneous disease with few modifiable risk factors, characterized by multiple subtypes that influence different populations with varying incidence, morbidity and mortality. Though recent genomic advances have enabled the stratification of breast cancer into numerous subtypes with differing therapeutic and prognostic values, it remains unclear why the incidence and outcome of certain breast cancers show an uneven distribution across different race/ethnic populations. For example, the higher frequency of more aggressive forms of breast cancer in young women of African descent is well known, yet why this occurs remains to be determined. To understand the mechanisms of breast cancer health disparity, we performed a molecular and genomic profiling on a unique cohort of racially diverse breast cancer patients from a catchment area in the northern part of east North Carolina and found earlier onset of breast cancer in women of African Ancestry (AA) with 32.1 % occurring before age 50 compared to 22.5 % for women of European Ancestry (EA). Furthermore, women of AA have higher levels of obesity with 35.5 % having a Body mass index (BMI) above 35 compared to 17.9 % for women of EA. Notably, women of AA also showed presence of higher stage of breast cancer with more than 26 % having stage 3 or 4 compared to 16.5 % for women of EA. We also found that women of AA showed poorer overall survival outcome from breast cancer compare to EA with Hazard Ratio of 1.67. The panel of exome sequencing of 147 tumors from this cohort revealed differential mutational frequencies in African Ancestry versus European Ancestry. The insertion/deletion mutated genes found only in African Ancestry included PAX5, CYP2A7, UGT2B17, CYP4A11, ACAA1, KIT and NAT2 with high percentage of cases with mutation account, whereas those genes unique to European Ancestry included GSTP1, PRSS53, AURKA, ATF1, BIRC2, PGAP3 and GSTA4. In addition to this, there are differentially mutated genes across specific breast cancer subtypes where ABL2, UBA1, CYP4F8, PIK3CG, CTNNA1, CYP39A1 genes are only associated with Triple Negative Breast Cancer patients. By characterizing the risk of breast cancer among ethnically diverse groups, we provide needed insights that will not only improve the development of personalized prognostic and predictive biomarkers but may also enhance breast cancer screening, treatment, survival and prevention. Citation Format: Jung S. Byun, Tingfen Yan, Adam Sowalsky, Jack Zhu, Paul Meltzer, Nasreen Vohra, Peter Kragel, Anna Napoles, Eliseo Perez-Stable, Kevin Gardner. Characterizing breast cancer health disparities through molecular and genomic profiling of a diverse breast cancer cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4246.