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 integr...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.展开更多
文摘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.
