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Purpose <p>Brain metastases (BM) in patients with metastatic breast cancer (MBC) cause significant morbidity/mortality. A relatively high prevalence of BM is seen in patients with germline <i>BRCA1/2</i> mutations. Some patients with MBC have somatic <i>BRCA1/2</i> mutations but the prevalence of BM in this setting is not known.</p> Methods <p>Here, we evaluated the prevalence and clinical and genomic characteristics of BM in patients with MBC with somatic <i>BRCA1/2</i> mutations in cell-free DNA (cfDNA) using the Guardant360 assay. Clinical and genomic features of patients with somatic <i>BRCA1/2</i> mutations and brain metastases, and those without brain metastases were compared using a Chi-squared test for categorical variables and Wilcoxon rank-sum test for continuous variables.</p> Results <p>Of 36 patients with MBC and somatic <i>BRCA1/2</i> mutations, 9 (25%) developed BM. The median time to development of BM was 6.7&#xa0;months after somatic <i>BRCA</i> detection by cfDNA testing. Among patients with BM, somatic <i>BRCA</i> mutations were commonly <i>BRCA1</i>, clonal, and present at a higher mutant allelic fraction. The coexisting genomic landscape in patients with BM commonly included <i>PIK3CA, TP53, MYC, EGFR, CCNE1,</i> and <i>KIT</i> mutations.</p> Conclusion <p>A relatively high prevalence of BM in patients with MBC harboring cfDNA somatic <i>BRCA1/2</i> mutations was observed. CfDNA somatic <i>BRCA1/2</i> mutations may help identify patients with MBC at risk for BM. To our knowledge, this is the first report linking cfDNA somatic <i>BRCA</i> mutations with BM, and requires further investigation in additional datasets and studies.</p>

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Brain metastases in patients with metastatic breast cancer and BRCA1/2 mutations in cell-free DNA

  • 期刊论文

  • 发表日期：

    2025年4月25日

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  • Neelima Vidula,
  • Erica Blouch,
  • Katherine Hesler,
  • Andrzej Niemierko,
  • Aditya Bardia

摘要

Purpose

Brain metastases (BM) in patients with metastatic breast cancer (MBC) cause significant morbidity/mortality. A relatively high prevalence of BM is seen in patients with germline BRCA1/2 mutations. Some patients with MBC have somatic BRCA1/2 mutations but the prevalence of BM in this setting is not known.

Methods

Here, we evaluated the prevalence and clinical and genomic characteristics of BM in patients with MBC with somatic BRCA1/2 mutations in cell-free DNA (cfDNA) using the Guardant360 assay. Clinical and genomic features of patients with somatic BRCA1/2 mutations and brain metastases, and those without brain metastases were compared using a Chi-squared test for categorical variables and Wilcoxon rank-sum test for continuous variables.

Results

Of 36 patients with MBC and somatic BRCA1/2 mutations, 9 (25%) developed BM. The median time to development of BM was 6.7 months after somatic BRCA detection by cfDNA testing. Among patients with BM, somatic BRCA mutations were commonly BRCA1, clonal, and present at a higher mutant allelic fraction. The coexisting genomic landscape in patients with BM commonly included PIK3CA, TP53, MYC, EGFR, CCNE1, and KIT mutations.

Conclusion

A relatively high prevalence of BM in patients with MBC harboring cfDNA somatic BRCA1/2 mutations was observed. CfDNA somatic BRCA1/2 mutations may help identify patients with MBC at risk for BM. To our knowledge, this is the first report linking cfDNA somatic BRCA mutations with BM, and requires further investigation in additional datasets and studies.