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

被引：0

作者：

Huebner, Hanna ^{[1
,2
]}

Wimberger, Pauline ^{[3
,4
,5
,6
,7
,8
,9
]}

Laakmann, Elena ^{[10
]}

Ruckhaeberle, Eugen ^{[11
]}

Ruebner, Matthias ^{[1
,2
]}

Lehle, Sarah ^{[1
,2
]}

Uhrig, Sabrina ^{[1
,2
]}

Ziegler, Philipp ^{[1
,2
]}

Link, Theresa ^{[3
,4
,5
,6
,7
,8
,9
]}

Hack, Carolin C. ^{[1
,2
]}

Belleville, Erik ^{[12
]}

Faull, Iris ^{[13
]}

Hausch, Marcus ^{[13
]}

Wallwiener, Diethelm ^{[14
]}

Schneeweiss, Andreas ^{[15
]}

Tesch, Hans ^{[16
]}

Brucker, Sara Y. ^{[14
]}

Beckmann, Matthias W. ^{[1
,2
]}

Fasching, Peter A. ^{[1
,2
]}

Mueller, Volkmar ^{[10
]}

Fehm, Tanja N. ^{[11
]}

机构：

[1] Friedrich Alexander Univ Erlangen Nuremberg, Erlangen Univ Hosp, Comprehens Canc Ctr Erlangen EMN, Dept Gynecol & Obstet, D-91054 Erlangen, Germany

[2] Bavarian Canc Res Ctr BZKF, D-91054 Erlangen, Germany

[3] Carl Gustav Carus Fac Med, Dept Gynecol & Obstet, D-01307 Dresden, TU, Germany

[4] Univ Hosp, D-01307 Dresden, TU, Germany

[5] Natl Ctr Tumor Dis NCT, D-01307 Dresden, Germany

[6] German Canc Res Ctr, D-69120 Heidelberg, Germany

[7] Carl Gustav Carus Fac Med, D-01307 Dresden, TU, Germany

[8] Helmholtz Zentrum Dresden Rossendorf HZDR, D-01307 Dresden, Germany

[9] German Canc Consortium DKTK, D-01307 Dresden, Germany

[10] Hamburg Eppendorf Univ, Dept Gynecol, Med Ctr, D-20246 Hamburg, Germany

[11] Univ Hosp Dusseldorf, Dept Gynecol & Obstet, CIO ABCD, D-40225 Dusseldorf, Germany

[12] ClinSol GmbH & Co KG, D-97074 Wurzburg, Germany

[13] Guardant Hlth Inc, Redwood City, CA 94063 USA

[14] Univ Tubingen, Dept Obstet & Gynecol, D-72076 Tubingen, Germany

[15] Heidelberg Univ Hosp, Natl Ctr Tumor Dis, German Canc Res Ctr DKFZ, D-69120 Heidelberg, Germany

[16] Oncol Practice Bethanien Hosp Frankfurt, D-60389 Frankfurt, Germany

来源：

PRECISION CLINICAL MEDICINE | 2025年 / 8卷 / 01期

关键词：

ctDNA; cfDNA; cell-free DNA; breast cancer; genetic testing; PHASE-II; ESR1; MUTATIONS; CAPIVASERTIB; FULVESTRANT; INHIBITOR; BRCA1/2; THERAPY;

D O I：

10.1093/pcmedi/pbae034

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页数：12

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