Cell-free tumor DNA analysis in advanced or metastatic breast cancer patients: mutation frequencies, testing intention, and clinical impact.

IF 5.1 4区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Precision Clinical Medicine Pub Date : 2024-12-24 eCollection Date: 2025-03-01 DOI:10.1093/pcmedi/pbae034

Hanna Huebner, Pauline Wimberger, Elena Laakmann, Eugen Ruckhäberle, Matthias Ruebner, Sarah Lehle, Sabrina Uhrig, Philipp Ziegler, Theresa Link, Carolin C Hack, Erik Belleville, Iris Faull, Marcus Hausch, Diethelm Wallwiener, Andreas Schneeweiss, Hans Tesch, Sara Y Brucker, Matthias W Beckmann, Peter A Fasching, Volkmar Müller, Tanja N Fehm

{"title":"Cell-free tumor DNA analysis in advanced or metastatic breast cancer patients: mutation frequencies, testing intention, and clinical impact.","authors":"Hanna Huebner, Pauline Wimberger, Elena Laakmann, Eugen Ruckhäberle, Matthias Ruebner, Sarah Lehle, Sabrina Uhrig, Philipp Ziegler, Theresa Link, Carolin C Hack, Erik Belleville, Iris Faull, Marcus Hausch, Diethelm Wallwiener, Andreas Schneeweiss, Hans Tesch, Sara Y Brucker, Matthias W Beckmann, Peter A Fasching, Volkmar Müller, Tanja N Fehm","doi":"10.1093/pcmedi/pbae034","DOIUrl":null,"url":null,"abstract":"Background: Circulating cell-free tumor DNA (ctDNA) provides a non-invasive approach for assessing somatic alterations. The German PRAEGNANT registry study aims to explore molecular biomarkers and investigate their integration into clinical practice. In this context, ctDNA testing was included to understand the motivations of clinicians to initiate testing, to identify somatic alterations, and to assess the clinical impact of the results obtained.Methods: Patients with advanced/metastatic breast cancer were prospectively enrolled in the Prospective Academic Translational Research Network for the Optimization of Oncological Health Care Quality in the Adjuvant and Advanced/Metastatic Setting (PRAEGNANT study; NCT02338167). The FDA-approved and CE-marked GUARDANT360 CDx test was used to assess somatic alterations. A ctDNA-analysis report was provided to the treating physician along with a questionnaire about the intent for testing and the clinical implications of test results.Results: ctDNA from 49 patients was analyzed prospectively: 37 (76%) had at least one somatic alteration in the analyzed geneset; 14 patients (29%) harbored alterations in TP53, 12 (24%) in PIK3CA, and 6 (12%) in ESR1. Somatic mutations in BRCA1 or BRCA2 were detected in 3 (6%) and 4 (8%) patients, respectively, and 59% of patients had hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. Questionnaires regarding test intentions and clinical impact were completed for 48 (98%) patients. These showed that ctDNA testing influenced treatment decisions for 35% of patients.Discussion: The high prevalence of somatic alterations in TP53, PIK3CA, ESR1, and BRCA1/2 genes, identified by ctDNA genotyping, highlights their potential as biomarkers for targeted therapies. Detection of specific mutations affected treatment decisions, such as eligibility for alpelisib, and might further facilitate treatment with e.g. elacestrant or capiversatib in future treatment lines.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"8 1","pages":"pbae034"},"PeriodicalIF":5.1000,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748133/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Precision Clinical Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/pcmedi/pbae034","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Circulating cell-free tumor DNA (ctDNA) provides a non-invasive approach for assessing somatic alterations. The German PRAEGNANT registry study aims to explore molecular biomarkers and investigate their integration into clinical practice. In this context, ctDNA testing was included to understand the motivations of clinicians to initiate testing, to identify somatic alterations, and to assess the clinical impact of the results obtained.

Methods: Patients with advanced/metastatic breast cancer were prospectively enrolled in the Prospective Academic Translational Research Network for the Optimization of Oncological Health Care Quality in the Adjuvant and Advanced/Metastatic Setting (PRAEGNANT study; NCT02338167). The FDA-approved and CE-marked GUARDANT360 CDx test was used to assess somatic alterations. A ctDNA-analysis report was provided to the treating physician along with a questionnaire about the intent for testing and the clinical implications of test results.

Results: ctDNA from 49 patients was analyzed prospectively: 37 (76%) had at least one somatic alteration in the analyzed geneset; 14 patients (29%) harbored alterations in TP53, 12 (24%) in PIK3CA, and 6 (12%) in ESR1. Somatic mutations in BRCA1 or BRCA2 were detected in 3 (6%) and 4 (8%) patients, respectively, and 59% of patients had hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. Questionnaires regarding test intentions and clinical impact were completed for 48 (98%) patients. These showed that ctDNA testing influenced treatment decisions for 35% of patients.

Discussion: The high prevalence of somatic alterations in TP53, PIK3CA, ESR1, and BRCA1/2 genes, identified by ctDNA genotyping, highlights their potential as biomarkers for targeted therapies. Detection of specific mutations affected treatment decisions, such as eligibility for alpelisib, and might further facilitate treatment with e.g. elacestrant or capiversatib in future treatment lines.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

晚期或转移性乳腺癌患者的无细胞肿瘤DNA分析：突变频率、检测意图和临床影响。

背景：循环无细胞肿瘤DNA （ctDNA）为评估体细胞改变提供了一种无创方法。德国PRAEGNANT注册研究旨在探索分子生物标志物并研究其与临床实践的结合。在这种情况下，ctDNA测试包括了解临床医生启动测试的动机，识别体细胞改变，并评估所获得结果的临床影响。方法：晚期/转移性乳腺癌患者被前瞻性纳入前瞻性学术转化研究网络，以优化辅助和晚期/转移性环境中的肿瘤医疗质量（PRAEGNANT研究）；NCT02338167)。fda批准和ce认证的GUARDANT360 CDx检测用于评估体细胞改变。向治疗医生提供了一份ctdna分析报告，并提供了一份关于测试意图和测试结果临床意义的问卷。结果：前瞻性分析了49例患者的ctDNA: 37例（76%）在分析的基因集中至少有一个体细胞改变；14名患者（29%）携带TP53基因改变，12名（24%）携带PIK3CA基因改变，6名（12%）携带ESR1基因改变。分别在3例（6%）和4例（8%）患者中检测到BRCA1或BRCA2体细胞突变，59%的患者患有激素受体阳性、人表皮生长因子受体2阴性的乳腺癌。48例（98%）患者完成了关于测试意图和临床影响的问卷调查。这些研究表明，ctDNA检测影响了35%的患者的治疗决策。讨论：通过ctDNA基因分型发现，TP53、PIK3CA、ESR1和BRCA1/2基因的体细胞改变非常普遍，这凸显了它们作为靶向治疗生物标志物的潜力。特定突变的检测会影响治疗决策，例如alpelisib的使用资格，并可能进一步促进在未来的治疗品系中使用elacestrant或capitavitb进行治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Precision Clinical Medicine MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

10.80

自引率

0.00%

发文量

审稿时长

5 weeks

期刊介绍： Precision Clinical Medicine (PCM) is an international, peer-reviewed, open access journal that provides timely publication of original research articles, case reports, reviews, editorials, and perspectives across the spectrum of precision medicine. The journal's mission is to deliver new theories, methods, and evidence that enhance disease diagnosis, treatment, prevention, and prognosis, thereby establishing a vital communication platform for clinicians and researchers that has the potential to transform medical practice. PCM encompasses all facets of precision medicine, which involves personalized approaches to diagnosis, treatment, and prevention, tailored to individual patients or patient subgroups based on their unique genetic, phenotypic, or psychosocial profiles. The clinical conditions addressed by the journal include a wide range of areas such as cancer, infectious diseases, inherited diseases, complex diseases, and rare diseases.