npj Breast Cancer (Apr 2023)

Utilizing cell-free DNA to predict risk of developing brain metastases in patients with metastatic breast cancer

  • Neelima Vidula,
  • Andrzej Niemierko,
  • Katherine Hesler,
  • Lianne Ryan,
  • Beverly Moy,
  • Steven Isakoff,
  • Leif Ellisen,
  • Dejan Juric,
  • Aditya Bardia

DOI
https://doi.org/10.1038/s41523-023-00528-z
Journal volume & issue
Vol. 9, no. 1
pp. 1 – 6

Abstract

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Abstract We compared cell-free DNA (cfDNA) results at MBC diagnosis in patients who developed brain metastases (BM) vs those without (non-BM) to understand genomic predictors of BM. Patients with cfDNA testing at MBC diagnosis (Guardant360®, 73 gene next generation sequencing) were identified. Clinical and genomic features of BM and non-BM were compared (Pearson’s/Wilcoxon rank sum tests). Eighteen of 86 patients (21%) with cfDNA at MBC diagnosis developed BM. Comparing BM vs non-BM, a higher prevalence of BRCA2 (22% vs 4.4%, p = 0.01), APC (11% vs 0%, p = 0.005), CDKN2A (11% vs 1.5%, p = 0.05), and SMAD4 (11% vs 1.5%, p = 0.05) was observed. Seven of 18 BM had ≥1 of the following 4 mutations in baseline cfDNA: APC, BRCA2, CDKN2A or SMAD4 vs 5/68 non-BM (p = 0.001). Absence of this genomic pattern had a high negative predictive value (85%) and specificity (93%) in excluding BM development. Baseline genomic profile varies in MBC that develops BM.