Neelima Vidula, Erica Blouch, Katherine Hesler, Andrzej Niemierko, Aditya Bardia
{"title":"转移性乳腺癌和无细胞DNA BRCA1/2突变患者的脑转移。","authors":"Neelima Vidula, Erica Blouch, Katherine Hesler, Andrzej Niemierko, Aditya Bardia","doi":"10.1007/s10549-025-07705-7","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"107-112"},"PeriodicalIF":3.0000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Brain metastases in patients with metastatic breast cancer and BRCA1/2 mutations in cell-free DNA.\",\"authors\":\"Neelima Vidula, Erica Blouch, Katherine Hesler, Andrzej Niemierko, Aditya Bardia\",\"doi\":\"10.1007/s10549-025-07705-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":9133,\"journal\":{\"name\":\"Breast Cancer Research and Treatment\",\"volume\":\" \",\"pages\":\"107-112\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2025-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Breast Cancer Research and Treatment\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s10549-025-07705-7\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/4/25 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Breast Cancer Research and Treatment","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10549-025-07705-7","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/25 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
Brain metastases in patients with metastatic breast cancer and BRCA1/2 mutations in cell-free DNA.
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.
期刊介绍:
Breast Cancer Research and Treatment provides the surgeon, radiotherapist, medical oncologist, endocrinologist, epidemiologist, immunologist or cell biologist investigating problems in breast cancer a single forum for communication. The journal creates a "market place" for breast cancer topics which cuts across all the usual lines of disciplines, providing a site for presenting pertinent investigations, and for discussing critical questions relevant to the entire field. It seeks to develop a new focus and new perspectives for all those concerned with breast cancer.