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Genetic Diversity in Breast Cancer: Unveiling Racial Differences in Mutation Profiles 

Clinical Genetics and Therapeutics
  • Primary Categories:
    • Clinical Genetics
  • Secondary Categories:
    • Clinical Genetics
Introduction:
Breast cancer affects 1 in 10 women and has a lifetime diagnosis risk of 13% for U.S. women. Subtypes include Luminal A, Luminal B, and triple-negative, with African American women facing higher rates of the aggressive triple-negative subtype and higher mortality rates despite similar diagnostic rates to white women. Research suggests that socio-economic factors and molecular differences largely drive this difference. Increasing access to genetic analysis has facilitated a deeper understanding of potential genetic factors contributing to disparities in breast cancer outcomes across racial groups. In this study, we examine somatic mutation data for breast cancer patients, focusing on 50 cancer-hit genes often implicated in oncogenesis.  By investigating this large subset of genetic factors, this research further investigates molecular differences and aims to advance personalized treatments to improve outcomes in this community.

 

Methods:
The study uses data from Prisma Health Cancer Center Biorepository (Greenville, SC, USA) collected between 2012 and 2021, with 194 breast cancer specimens (161 White, 33 African American), screened for mutations by Precision Genetics.  Analyzed genes include 10 tumor suppressors, 33 oncogenes, and 7 context-dependent genes. Patient data from the Prisma Health Cancer Institute database and EPIC®, including demographic details such as age, race, sex, and smoking status, along with tumor characteristics like tissue site, histology, grade, and TNM staging. Our analysis assessed racial differences in mutation frequency, molecular-subtype, and specific amino acid substitutions in each gene.

 

Results:
The dataset shows that PIK3CA mutations (29%) are the most frequently mutated among these patients followed by KDR mutations (21%), and TP53 mutations (12%).  Racial differences were found in mutation frequencies, notably in the PIK3CA, KDR, TP53, KIT, and MET genes. JAK3 mutations showed a significant (p < 0.001) racial difference with higher prevalence in African Americans (24%) compared to Whites (2%). Specific mutations varied by race: PIK3CA p.His1047Arg was more common in Whites (30% White, none in African Americans), while p.Ile391Met was higher in African Americans (24% White, 79% African American). In the total population, ER+/PR+ breast cancer is the most prevalent subtype (69.90%), followed by triple-negative breast cancer (19.39%), ER+ only cases (9.69%), and PR+ only cases (1.02%).  African Americans had a higher prevalence of triple-negative breast cancer (TNBC), associated with poorer outcomes (11% White, 27% African American, p <0.05). African American TNBC samples showed a higher prevalence of PIK3CA (29%) and JAK3 (23%) mutations, while White TNBC samples had more frequent mutations in TP53 (30%) and KDR (23%) Overall mutation rates across all genes were similar (81% White, 82% African American).

 

Conclusion:
While overall mutation rates are comparable, mutations and subtype frequencies differ between African American and White patients. This detailed analysis of specific amino acid substitutions provides valuable insights into distinct mutation patterns across racial groups, deepening our understanding of the molecular mechanisms that may drive the differences in outcomes. These results emphasize the need for personalized breast cancer treatments that consider genetic variability. Including African American women in clinical trials is crucial, as understanding these molecular differences could lead to tailored therapies and improved survival, especially in African American women who are historically underrepresented in research.

 

Agenda

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