Circulating Tumor DNA in Early and Metastatic Breast Cance—Current Role and What Is Coming Next.

Simple Summary: Liquid biopsy, particularly involving the detection of circulating tumor DNA (ctDNA), has emerged as a promising tool in breast cancer management. Unlike traditional tissue biopsies, ctDNA provides a non-invasive method by detecting DNA fragments released by tumor cells into the bloodstream. Detection techniques include PCR-based methods, targeted panels for known mutations, and personalized assays based on the individual tumor profile. In early-stage breast cancer, ctDNA shows potential for assessing response to treatments like chemotherapy and identifying patients at elevated risk of recurrence. However, ctDNA detection in early-stage disease remains challenging due to low tumor DNA concentrations in blood. In metastatic breast cancer, ctDNA is utilized to monitor disease progression, evaluate treatment response, and detect emerging resistance mutations, enabling timely adjustments in therapy. Although ctDNA holds significant potential for enhancing personalized care, further research is necessary to validate its role in routine clinical practice for comprehensive breast cancer management. The progress that has been made in recent years in relation to liquid biopsies in general and circulating tumor DNA (ctDNA) in particular can be seen as groundbreaking for the future of breast cancer treatment, monitoring and early detection. Cell-free DNA (cfDNA) consists of circulating DNA fragments released by various cell types into the bloodstream. A portion of this cfDNA, known as ctDNA, originates from malignant cells and carries specific genetic mutations. Analysis of ctDNA provides a minimally invasive method for diagnosis, monitoring response to therapy, and detecting the emergence of resistance. Several methods are available for the analysis of ctDNA, each with distinct advantages and limitations. Quantitative polymerase chain reaction is a well-established technique widely used due to its high sensitivity and specificity, particularly for detecting known mutations. In addition to the detection of individual mutations, multigene analyses were developed that could detect several mutations at once, including rarer mutations. These methods are complementary and can be used strategically depending on the clinical question. In the context of metastatic breast cancer, ctDNA holds particular promise as it allows for the dynamic monitoring of tumor evolution. Through ctDNA analysis, mutations in the ESR1 or PIK3CA genes, which are associated with therapy resistance, can be identified. This enables the early adjustment of treatment and has the potential to significantly enhance clinical outcome. The application of ctDNA in early breast cancer is an ongoing investigation. In (neo)adjuvant settings, there is preliminary data indicating that ctDNA can be used for therapy monitoring and risk stratification to decide on post-neoadjuvant strategies. In the monitoring of aftercare, the detection of ctDNA appears to be several months ahead of routine imaging. However, the feasibility of implementing this approach in a clinical setting remains to be seen. While the use of ctDNA as a screening method for the asymptomatic population would be highly advantageous due to its minimally invasive nature, the available data on its clinical benefit are still insufficient. Nevertheless, ctDNA represents the most promising avenue for fulfilling this potential future need. [ABSTRACT FROM AUTHOR]