The Potential Use of Urinary CtDNA Profiling in the Treatment of Breast Cancer

Cell-free circulating tumor DNA (ctDNA), shed into the blood stream by apoptotic or necrotic tumor cells of either primary or metastatic sites, became an extensively investigated and very promising analyte in oncology research. If passing through the kidney barrier, ctDNA is likely to occur in urine. Literature research revealed a lack of studies aiming at diagnostic use of urinary ctDNA. Most studies investigating urinary ctDNA were performed in the field of urological cancers emphasizing, however, that urinary liquid biopsies were suitable to draw conclusive real time pictures of ctDNA alterations coming from circulation and hence strengthen the hypothesis that genetic profiling of urinary ctDNA could be valuable to gain tumor-related information also in other solid tumors such as breast cancer. Usually, clinical treatment decisions are based on mutation profiles that were received from initial tissue biopsies. Though, during therapy the genetic tumor profile might change e.g. gain and loss of genetic alterations that might be relevant for targeted therapy options or treatment resistance. Particularly patients with advanced breast cancer may acquire mutations during treatment cycles and might benefit from serial ctDNA sequencing to find new targetable mutations and gain access to tailored therapy. Here, the use of urinary ctDNA might offer an opportunity for non-invasive longitudinal genotyping and testing for actionable mutations. In contrast to plasma-derived ctDNA, only a few studies were performed using urinary ctDNA from patients with breast cancer and revealed that targeted NGS appeared to be a sensitive method to detect tumor-specific genetic features. In this mini review we sought to illuminate the potential use of urinary ctDNA for longitudinal disease monitoring at frequent intervals and low effort for patients with breast cancer.

Keywords: Breast cancer; Mutation profiling; Urinary ctDNA; NGS; Targeted therapy; Disease monitoring; Recurrence; Resistance

Abbreviations: cfDNA: cell free circulating DNA; ctDNA: cell free circulating tumor DNA; CNV: Copy Number Variation; SNV: Single Nucleotide Variant; ER: Estrogen Receptor; PR: Progesterone Receptor; HER2: Human Epidermal growth factor Receptor-2; ddPCR: digital droplet PCR; NGS: Next Generation Sequencing; PIK3CA: Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha; TP53: Tumor protein p53; CDH1: Cadherin-1; MLL3: Myeloid/lymphoid or mixed-lineage leukemia protein 3; ESR1: Estrogen Receptor 1; BRCA 1/2: Breast Cancer ½; DTC: Disseminated Tumor Cell