Distinct Molecular Differences Between African American/Black and White Women with Triple Negative Breast Cancer
Authors: So Hyeon Park, Roy Khalife, Evan White, Anthony Magliocco
Journal: Cancer Research | Volume 83, Issue 5
Publisher: The American Association for Cancer Research
Abstract P5-03-05:
Introduction: Triple-negative breast cancer (TNBC) is an aggressive disease that lacks well-defined molecular targets. It accounts for 15-20% of all breast cancers and disproportionately affects women of color due to both limited access to treatment and genetic variation. Recent studies identified BRCA1(or 2) and the PIK3CA/AKT1/PTEN axis as targets for treatment, but these studies neglected to account for genetic variations between race. Here, we present molecular differences between African American/Black (AA) and White (W) women with TNBC to highlight the importance of accounting for race to develop effective therapy and improve long-term outcomes. Methods: This study utilized the TCGA Firehose Legacy Breast Carcinoma dataset on cBioPortal. Subjects with breast cancer and negative ER, PR, and HER2 scores were stratified into AA (n=32) and W (n=69) subgroups. Data was analyzed to compare the most altered genes, copy number variation (CNV), and survival rates between the subgroups. The logrank test was used to obtain the hazard rate. The GISTIC2 model was used to assess CNV and G-scores (G; amplitude of aberration x frequency of occurrence). Results: The main genetic differences were in PIK3CA and BRCA1(or 2) genes. PIK3CA was detected as one of the ten most altered genes in TNBC, but this alteration was found in less than 10% of the TNBC cases. Of the 10%, PIK3CA was altered in 19% of W and 9% of AA subgroup. BRCA1(2) were altered in 10%(7%) of W but 0%(3%) of AA. Additionally, structural differences in chromosomes contributed to different survival outcomes. Both groups had co-amplification in 8q, but a significant hazard rate difference (z = 5.32, p < 0.001) was found for the W compared to the AA for the MYC gene. Further, the W had significantly higher amplification at 3q (G = 0.8 in W; 0.45 in AA). It is important to note that the PIK3CA gene lies in the 3q.26 region, meaning this gene is amplified significantly in the W subgroup. The AA group had a significant deletion at 8p.23 (G=0.5 in W; 0.8 in AA). Deletion of 8p causes MYC amplification, a targetable alteration. Conclusion: Our analysis reveals critical differences between AA and W subgroups with TNBC. Thus, it is clear that targeting the PIK3CA or BRCA1(2) gene benefits the W more than the AA population. To alleviate the disproportionate burden that AA women with TNBC face, more effort must be geared to find solutions specific to the AA subgroup. A greater sample size will help determine whether MYC amplification is unique to the AA subgroup, and if so, it could be targeted to improve outcomes of AA women with TNBC. Nevertheless, more data and research is needed to understand causes and decrease the rate of disparate outcomes in patients with TNBC.
https://aacrjournals.org/cancerres/article/83/5_Supplement/P5-03-05/716888