BC-Monitor: Towards a Routinely Accessible Circulating Tumor DNA-Based Tool for Real-Time Monitoring Breast Cancer Progression and Treatment Effectiveness

Abstract

Circulating tumor DNA (ctDNA) is increasingly employed in the screening, follow-up, and monitoring of the continuously evolving tumor; however, most ctDNA assays validated for clinical use cannot maintain the right balance between sensitivity, coverage, sample requirements, time, and cost. Here, we report our BC-monitor, a simple, well-balanced ctDNA diagnostic approach using a gene panel significant in breast cancer and an optimized multiplex PCR-based NGS protocol capable of identifying allele variant frequencies below 1% in cell-free plasma DNA. We monitored a cohort of 45 breast cancer patients prospectively enrolled into our study receiving neoadjuvant chemotherapy or endocrine therapy or palliative therapy for metastatic diseases. Their tumor mutation status was examined in the archived tumor samples and plasma samples collected before and continuously during therapy. Traceable mutations of the used 38-plex NGS assay were found in approximately two-thirds of the patients. Importantly, we detected new pathogenic variants in follow-up plasma samples that were not detected in the primary tumor and baseline plasma samples. We proved that the BC-monitor can pre-indicate disease progression four–six months earlier than conventional methods. Our study highlights the need for well-designed ctDNA monitoring during treatment and follow-up, integrated into a real-time treatment assessment, which could provide information on the active tumor DNA released into the blood.

BC-miR: Monitoring Breast Cancer-Related miRNA Profile in Blood Sera—A Prosperous Approach for Tumor Detection

“…Serum biomarkers have the potential to recognize the tumor even in its very early stage—tumor extension is 10–15 mm without any metastases—when it can be treated with a high prevalence and without a possible recurrence [ 4 , 5 ]. This assumption has been supported by a recently published article about monitoring circulating tumor DNA (ctDNA) from plasma and highlighting the importance of this technology in pre-indicative breast cancer management [ 6 ].…”

The Crucial Findings Derived from the Special Issue “Inside Cancer Genomics: From Structure to Therapy”

“…Priskin et al [ 22 ] addressed an important question regarding routine laboratory activities and tested a self-developed NGS panel in a prospective pilot study of high-risk breast cancer patients in the environment of routine practice. The panel covers 38 regions of 12 genes ( AKT1 , CDH1 , EGFR , ESR1 , FGFR1 , 156 FGFR4 , HER2 , HRAS , KRAS , MET , PIK3CA , TP53 ), selected on the basis of their high frequency in breast cancer, for their predictive or prognostic value, to guide targeted treatment, or underlie the most frequent resistance cases.…”