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Differences in the mutational landscape of triple-negative breast cancer in African Americans and Caucasians

  • Epidemiology
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Abstract

Background

Triple-negative breast cancer (TNBC) occurs at higher frequency in African Americans compared with Caucasians. It is unclear if the biology of TNBC is different in African American versus Caucasians. In this study, we sought to evaluate racial differences in the molecular pathology of TNBC.

Methods

Using data from The Cancer Genome Atlas, we identified TNBC patients with information on race. We analyzed differences in clinical characteristics, tumor somatic mutations, and gene expression patterns by race from whole exome and microarray data.

Results

1104 patients were identified, of which 178 had TNBC. TNBC was more frequent in African Americans than Caucasians (33.3 vs 14.9%). Although more African Americans than Caucasians overall were classified as basal-like from PAM50 gene expression (34.8 vs 16.1%), no differences in the TNBC cohort were observed. Median tumor somatic mutation counts were higher in African Americans versus Caucasians (39.5 vs 34), but no racial differences in the mutation counts in TNBC were observed. Somatic mutation analysis revealed racial differences in specific high prevalence genes in all patients (TP53 46% in African Americans vs 27% in Caucasians; PIK3CA 23% in African Americans vs 34% in Caucasians; and MLL3 12% in African Americans vs 6% in Caucasians). TNBC patients did not have any specific high prevalence genes associated with racial differences. There were no racial differences in gene expression patterns in selected genes involved in breast cancer biology. Overall, African Americans had shorter TTP and worse DFS. Racial differences in clinical outcomes were not observed in TNBC.

Conclusion

The mutational landscape of TNBC is similar between African Americans and Caucasians. The higher frequency of TNBC in African Americans is therefore not associated with a different genomic profile of commonly established tumor regulatory pathway genes. Other modifiable factors may exist that contribute to the racial disparity in TNBC.

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Funding

This study was funded by Grant Number 1K12CA167540 through the National Cancer Institute (NCI) at the National Institutes for Health (NIH) and Grant Number UL1 TR000448 through the Clinical and Translational Science Award (CTSA) program of the National Center for Advancing Translational Sciences (NCATS) at the NIH. The authors also wish to acknowledge the support of the Siteman Cancer Center Biostatistics Core and the NCI Cancer Center Support Grant P30 CA091842. The contents are solely the responsibility of the authors and do not necessarily represent the official view of the NCI, NCATS, or NIH.

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Authors and Affiliations

  1. Division of Oncology, Department of Medicine, Washington University in St. Louis School of Medicine, St. Louis, MO, 63110, USA

    Foluso O. Ademuyiwa, Katherine Weilbaecher & Cynthia X. Ma

  2. Division of Biostatistics, Washington University in St. Louis School of Medicine, St. Louis, MO, 63110, USA

    Yu Tao & Jingqin Luo

Authors
  1. Foluso O. Ademuyiwa
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Corresponding author

Correspondence to Foluso O. Ademuyiwa.

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Conflict of interest

Foluso Ademuyiwa, Yu Tao, Jingqin Luo, Cynthia Ma, and Katherine Weilbaecher declare no conflicts of interest.

Ethical approval

This article does not directly contain any studies with human participants performed by any of the authors. The results published here are in whole or part based upon data generated by TCGA managed by the NCI and NHGRI. Information about TCGA can be found at http://cancergenome.nih.gov.

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Informed consent was obtained from all individual participants included in TCGA.

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Ademuyiwa, F.O., Tao, Y., Luo, J. et al. Differences in the mutational landscape of triple-negative breast cancer in African Americans and Caucasians. Breast Cancer Res Treat 161, 491–499 (2017). https://doi.org/10.1007/s10549-016-4062-y

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  • DOI: https://doi.org/10.1007/s10549-016-4062-y

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