Huebner Hanna, Wimberger Pauline, Laakmann Elena, Ruckhäberle Eugen, Ruebner Matthias, Lehle Sarah, Uhrig Sabrina, Ziegler Philipp, Link Theresa, Hack Carolin C, Belleville Erik, Faull Iris, Hausch Marcus, Wallwiener Diethelm, Schneeweiss Andreas, Tesch Hans, Brucker Sara Y, Beckmann Matthias W, Fasching Peter A, Müller Volkmar, Fehm Tanja N
Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University of Erlangen-Nuremberg, Erlangen 91054, Germany.
Bavarian Cancer Research Center (BZKF), Erlangen 91054, Germany.
Precis Clin Med. 2024 Dec 24;8(1):pbae034. doi: 10.1093/pcmedi/pbae034. eCollection 2025 Mar.
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.
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.
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 , 12 (24%) in , and 6 (12%) in . Somatic mutations in or 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.
The high prevalence of somatic alterations in , and 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.
循环游离肿瘤DNA（ctDNA）为评估体细胞改变提供了一种非侵入性方法。德国PRAEGNANT注册研究旨在探索分子生物标志物并研究将其整合到临床实践中的情况。在此背景下，纳入ctDNA检测以了解临床医生启动检测的动机、识别体细胞改变并评估所获结果的临床影响。
晚期/转移性乳腺癌患者被前瞻性纳入辅助及晚期/转移性环境下肿瘤医疗质量优化前瞻性学术转化研究网络（PRAEGNANT研究；NCT02338167）。使用经美国食品药品监督管理局（FDA）批准并带有欧洲合格认证（CE）标志的GUARDANT360 CDx检测来评估体细胞改变。一份ctDNA分析报告与一份关于检测意图及检测结果临床意义的问卷一同提供给主治医生。
对49例患者的ctDNA进行了前瞻性分析：37例（76%）在分析的基因集中至少有一处体细胞改变；14例患者（29%）在 中有改变，12例（24%）在 中有改变，6例（12%）在 中有改变。分别在3例（6%）和4例（8%）患者中检测到 或 中的体细胞突变，59%的患者患有激素受体阳性、人表皮生长因子受体2阴性乳腺癌。48例（98%）患者完成了关于检测意图和临床影响的问卷。这些问卷显示，ctDNA检测影响了35%患者的治疗决策。
通过ctDNA基因分型鉴定出的 、 和 基因中体细胞改变的高发生率，凸显了它们作为靶向治疗生物标志物的潜力。特定突变的检测影响了治疗决策，如阿培利司的适用性，并且在未来治疗方案中可能进一步促进使用例如艾拉司群或卡维地洛进行治疗。
