The Pitfalls of Next-Generation Sequencing: Revisiting the Importance of Clinical Actionable Results in Targeted Genomic Testing and Precision Oncology

With Next-Generation Sequencing having transformed genomic testing, its increased implementation has exposed major limitations, including signal degradation, variant miscallings in low-frequency signals, and errors in reading regions with Copy Number Variations (CNVs). As a result of this, data collected by such sequencing methods often are clinically inactionable and are vulnerable to misinterpretations, reflected in the disparity between the 7.4% of breast cancer patients who have undergone MP-guided treatment despite 62% of cases involving targetable genomic alterations identified through NGS. In response to this concern, Mammaprint has reinforced the value of targeted genomic profiling in precision oncology, highlighting the importance of more focused gene panels for obtaining results that provide clinical insight into suitable treatment pathways for patients. By translating data to binary results of “low risk” and “high risk”, leveraging Distant Free Metastasis Survival (DFMS) calculations as a key metric to display the expected outcomes and levels of efficacy in different treatment pathways, genomic testing tools like Mammaprint have displayed the importance of clinically actionable interpretation over broad genomic complexity in assisting informed decision-making in oncology.