Abstract P6-11-05: Tumor mutational profile of triple-negative breast cancer amongst hispanics of Mexican descent
Authors: Gaur Sumit , Philipovskiy Alexander , McAlice Meghan , Umeanaeto Onyedika V , Ghimire Kiran 
Published: March 2020

Introduction: Triple negative breast cancer (TNBC) is biologically defined by the absence of expression of ER, PR, and Her-2neu receptors and clinically has a poor prognosis. Racial disparities in breast cancer are well recognized with African-Americans and Hispanics having a higher prevalence of TNBC as compared to Caucasians. Advances in characterization of the molecular drivers of cancer hold the promise of better targeting TNBC and addressing some of the disparities in outcomes noted amongst minorities. However, based on the data from the cancer genome atlas (TCGA), the mutational landscape of TNBC in African-Americans was found to be similar to that of Caucasians. There is a remarkable lack of data regarding the genomic aberrations (GA) in TNBC in Hispanics. Of the more than 1000 breast cancer cases in the TCGA, only 37 are identified as Hispanic. Of these 37, only 4 had TNBC. Objective: Aim of the current study is to describe the GA seen in triple negative breast cancer patients, diagnosed at the Garbar Breast Cancer Center (GBCC) at TTUHSC-EP which serves a predominantly Mexican-American Hispanic population. Methods: Medical records of patients diagnosed with triple negative breast cancer at GBCC were reviewed. Of these, ones who had undergone next generation sequencing of the tumor were selected for review. Clinical, pathological and demographic data was extracted. Results were compared with the GA reported in the TCGA basal like subtype and the METABRIC (molecular taxonomy of breast cancer international consortium) triple negative cohorts. Results: Next generation sequencing data of representative tumor specimen for the detection of substitutions, insertion and deletion alterations (indels), and copy number alterations (CNAs) in 324 genes and select gene rearrangements, as well as genomic signatures including microsatellite instability (MSI) and tumor mutational burden (TMB) using DNA isolated from formalin-fixed paraffin embedded (FFPE) tumor tissue specimens was available for 17 patients. All were Hispanic females of Mexican-American heritage. Median age is 54 years (range 23-88). 14 (82.3%) had stage IV and 3 (17.7%) had stage III cancer. Of the 11 patients who underwent germ-line testing for inherited cancer predisposition syndrome, only one was found to have a pathogenic BRCA mutation. Tumor mutational burden(TMB) could not be determined in 3 cases. The average TMB in the remaining 14 cases was 4.7 mutations/Mb (Range: 1-10). All tumors were micro satellite stable. The top 5 gene mutations seen and their corresponding frequency in TCGA and METABRIC database are shown in the following tables. Conclusions: In a predominantly Hispanic cohort of advanced TNBC, we found a 100% prevalence of TP53 mutations and an increased frequency of NF1 and PTEN mutations as compared to reported frequencies in TCGA and METABRIC database. All cases were micro satellite stable and had low TMB. This suggests that molecular drives of cancer may be different in Hispanics and a better understanding of these may help address some of the disparities seen in outcomes in this group of patients.

Frequency of 5 most commonly mutated genes seen at GBCC versus TCGAGeneGBCC (n=17)(%)TCGA(n-93)(%)pTP5310082.80.06NF117.62.150.004PIK3CA17.67.50.18PTEN17.61.080.0008RB111.74.30.21

Frequency of 5 most commonly mutated genes at GBCC vs METABRIC databaseGeneGBCC (n-17)(%)METABRIC (n-245)(%)pTP53100800.04NF117.63.270.004PIK3CA17.618.370.9PTEN17.66.50.08RB111.74.90.22

Citation Format: Sumit Gaur, Alexander Philipovskiy, Meghan McAlice, Onyedika V Umeanaeto, Kiran Ghimire. Tumor mutational profile of triple-negative breast cancer amongst hispanics of Mexican descent [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 P6-11-05.