Breast Tumor Genomic Characteristics Suggest More Aggressive Biology in African American vs White Women


Key Points

  • African American women had a higher frequency of TP53 mutation and basal tumors and greater intratumor genetic heterogeneity.
  • Racial differences in TP53 mutation, basal subtype, and triple-negative tumor prevalence contributed to an increased risk of recurrence in African American women. 

In a study reported in the Journal of Clinical Oncology, Keenan et al found that African American women with breast cancer had greater intratumor genetic heterogeneity, a higher frequency of TP53 mutation, and higher risk for basal tumors compared with white women, with the characteristics suggesting more aggressive tumor biology.

Study Details

The study included data from white and African American women with stages I to III breast cancer diagnosed from 1988 to 2013 and primary tumors from The Cancer Genome Atlas from 2010 to 2014. Exome sequencing data were obtained for 663 white and 105 African American women, and gene expression data were obtained for 711 and 159, respectively.

Differences in Genetic Characteristics

The African American women had more TP53 mutations (42.9% vs 27.6%, P = .003; odds ratio [OR] = 1.90, 95% confidence interval [CI] = 1.24–2.92 after adjustment for age and stage) and fewer PIK3CA mutations (20.0% vs 33.9%, P = .008; OR = 0.50, 95% CI = 0.30–0.83, after adjustment for age and stage).

Intratumor genetic heterogeneity, measured by the mutant-allele tumor heterogeneity (MATH) algorithm, was greater in African American women overall by 5.1 units (95% CI = 2.4–7.7) and in triple-negative tumors by 4.1 units (95% CI = 1.4–6.8).

On the PAM50 assay, African American women were more likely to have basal tumors (39.0% vs 18.6%, P < .001; adjusted OR = 2.70, 95% CI = 1.85–3.95) and less likely to have luminal A tumors (17.0% vs 34.7%, P < .001; adjusted OR = 0.39, 95% CI = 0.25–0.60). Among triple-negative subtypes, the African American women had more basal-like 1 (adjusted OR = 6.21, 95% CI = 1.53–25.25) and mesenchymal stem-like tumors (adjusted OR = 4.38, 95% CI = 1.01–18.97).

Recurrence Risk

The African American women had a higher risk of tumor recurrence (hazard ratio = 2.22, 95% CI = 1.05–4.67, after adjustment for age and stage). The significant difference persisted after additional adjustment for intratumor genetic heterogeneity (adjusted HR = 2.11, P = .04) but not after adjustment for TP53 mutation (adjusted HR = 1.93, P = .09), PAM50 basal subtype (adjusted HR = 1.48, P = .33), or triple-negative tumor prevalence (adjusted HR = 1.47, P = .32).

The investigators concluded, “African Americans had greater intratumor genetic heterogeneity and more basal gene expression tumors, even within triple-negative breast cancer. This pattern suggests more aggressive tumor biology in African Americans than whites, which could contribute to racial disparity in breast cancer outcome.”

Aditya Bardia, MD, MPH, of Massachusetts General Hospital Cancer Center and Harvard Medical School, is the corresponding author of the Journal of Clinical Oncology article.

The study was supported in part by a Jerry Younger Grant for Clinical and Translational Breast Cancer Research.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.