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Clinical applications of next-generation sequencing-based ctDNA analyses in breast cancer: defining treatment targets
Eva Valentina Klocker1, Samantha Hasenleithner2, Rupert Bartsch3
1Division of Oncology, Department of Internal Medicine, Medical University of Graz, Austria.
Abstract:
The advancements in the detection and characterization of circulating tumor DNA (ctDNA) have revolutionized precision medicine and are likely to transform standard clinical practice. The non-invasive nature of this approach allows for molecular profiling of the entire tumor entity, while also enabling real-time monitoring of the effectiveness of cancer therapies as well as the identification of resistance mechanisms to guide targeted therapy. Although the field of ctDNA studies offers a wide range of applications, including in early disease, in this review we mainly focus on the role of ctDNA in the dynamic molecular characterization of unresectable locally advanced and metastatic BC (mBC). Here, we provide clinical practice guidance for the rapidly evolving field of molecular profiling of mBC, outlining the current landscape of liquid biopsy applications and how to choose the right ctDNA assay. Additionally, we underline the importance of exploring the clinical relevance of novel molecular alterations that potentially represent therapeutic targets in mBC, along with mutations where targeted therapy is already approved. Finally, we present a potential roadmap for integrating ctDNA analysis into clinical practice.
Insights
Circulating tumor DNA (ctDNA) analysis offers non-invasive molecular profiling for metastatic breast cancer (mBC). This review guides ctDNA assay selection and integration into clinical practice for dynamic treatment monitoring and targeted therapy selection.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circulating tumor DNA (ctDNA) detection and characterization have significantly advanced precision medicine.
- Liquid biopsy offers a non-invasive method for comprehensive tumor profiling and real-time treatment monitoring.
Purpose of the Study:
- To provide clinical guidance for molecular profiling of metastatic breast cancer (mBC) using ctDNA.
- To outline the current applications of liquid biopsy and aid in selecting appropriate ctDNA assays for mBC management.
Main Methods:
- Review of current literature on ctDNA applications in unresectable locally advanced and metastatic breast cancer.
- Analysis of liquid biopsy landscape and ctDNA assay selection criteria.
- Exploration of novel molecular alterations and approved targeted therapies in mBC.
Main Results:
- ctDNA analysis enables dynamic molecular characterization of mBC.
- Liquid biopsy facilitates real-time monitoring of therapy effectiveness and identification of resistance mechanisms.
- Guidance is provided for choosing the right ctDNA assay and integrating analysis into clinical practice.
Conclusions:
- ctDNA analysis is poised to transform clinical practice in mBC management.
- Understanding ctDNA is crucial for guiding targeted therapy and adapting treatment strategies.
- A roadmap for integrating ctDNA analysis into routine clinical care is presented.
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