The Value of RNASeq in Addressing Breast Cancer Disparities Among Minority Populations: A Focus on African American Women

 

  • Authors: Catalina Esguerra, Roy Khalife, Shahla Masood, Anthony Magliocco

  • Presented at: San Antonio Breast Cancer Symposium 2024, San Antonio, TX

  • Journal: Clinical Cancer Research (2025) 31 (12_Supplement): P5-02-14.

  • Publisher: American Association for Cancer Research

  • Publication Date: 2025/6/13

Background:

Breast cancer is a heterogenous disease with diverse behavior, the basis of which is unclear. Breast cancer (BC) is a significant health concern for women globally, but it manifests with notable disparities across different ethnic groups. African American (AA) women experience a paradox in breast cancer—they have a lower incidence rate of breast cancer compared to their white counterparts, yet they suffer from a higher mortality rate. This disparity spotlights a gap in understanding the underlying biological factors contributing to these outcomes. Genetic factors play a crucial role in breast cancer risk and prognosis. In complement to DNA, RNA sequencing (RNASeq) is able to demystify these pathways. Unlike DNA sequencing, which provides static information about genetic mutations and variants, RNASeq offers dynamic insights into gene expression levels and patterns, revealing how genes are regulated and expressed in different tissues and conditions. There is a significant lack of research exploring gene expression and patterns prevalent in African American women and other minority groups. Methods: Differential expression was run on a pilot study of 10 subjects via RNAseq data. An AA BC group (n=5) and a White (W) BC group (n=5). When comparing W tumor to W normal, 2921 genes were significantly different; comparing AA tumor to AA normal, 4913 genes were significantly different. These lists were filtered to only contain log2fold changes of the absolute value of 3 or greater, which filtered W to 108 genes and AA to 149 genes. These lists were uploaded to NIH’s DAVID Bioinformatics, which provides functional annotation clustering. Results: Using NIH’s DAVID Bioinformatics, a general overview of the two racial groups was assessed. The W BC subgroup was characterized to have significant enrichment in oxidoreductase pathways. Genes highlighted are STEAP4, ACADL, ADH1A, ADH1C, AOX1, AKR1C1, CDO1, CYP3A5, MAOA, RRM2. This cluster is statistically significant demonstrated by a P-value of 2.6E-5 and a Benjamini value of 7.6E-3. The AA BC subgroup was characterized to have significant enrichment in genes involved with mitosis and cell proliferation. Genes identified under this subgroup are NEK2, NUF2, TPX2, ASPM, AURKA, AURKB, CDC20, CDCA8, CENPA, CENPF, and KLHL13. This cluster is statistically significant demonstrated by a P-value of 3.8E-7 and a Benjamini value of 2.1E-5. Outside of DAVID, significant genes were assessed for each racial group. The white group had significant mutations in EGFR, ESR1, FGF10/12/13, and IDH1. While the African American group had significant mutations in CDH1, CDK4, FGF7, FGF9, FGFR4, HRAS, KDM6A, MSH3, MSH6, and PTEN. Both groups were noted to have unique fusion patterns. Conclusion: Each subgroup exhibited unique key genes that were significantly upregulated or downregulated. While mutations in genes such as EGFR and ESR1 in the W group are extensively studied, several genes identified in the AA group, except for CDK4, require further research to elucidate their roles in breast cancer. According to the DAVID analysis, the AA BC group exhibited significant enrichment clusters under mitosis. CDK4/6 inhibitors, a popular BC treatment that targets cell proliferation, might be beneficial for AA women. However, since African American women also have a higher incidence of triple-negative BC, where CDK4/6i (HR+/HER2− monotherapy) is not indicated, the BC treatment guidelines for AA women can be unclear. Understanding unique gene signatures in African American women with breast cancer is essential. Incorporating novel technologies like RNASeq into treatment plans can help address disparities between populations. This approach can lead to more comprehensive BC prevention, diagnosis, and treatment strategies. Ultimately, this will not only improve outcomes for African American women but also enhance our overall understanding of breast cancer across diverse populations.

 
Anthony Magliocco