Next-Generation Sequencing for Advanced Breast Cancer: What the Way to Go?

ABSTRACT

The rapid implementation of precision medicine tools in diagnosing and treating breast cancer (BC) has widened the potential therapeutic options for patients. The applications of gene sequencing, including next-generation gene sequencing (NGS), have led to numerous questions on how to validate, implement, interpret, prioritize and operationalize precision medicine tools to deliver meaningful and impactful interventions. Limited benefit has been portended with earlier experiences of NGS-driven treatment, in BC. However, the development and use of frameworks of clinical actionability of genomic alterations, for example, detected with NGS, has resulted in better patient selection, and potentially higher therapeutic value. The European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets (ESCAT) is a framework that includes five tiers of clinical actionability, with tier 1 reserved for approved drugs with demonstrated benefits for targetable genomic alterations. The re-analysis of clinical studies by grouping the genomic alterations and matched drugs with ESCAT, in high vs lower tiers has demonstrated a significant benefit portended by high tiers alterations, with the availability of efficacious treatments. As a result, frameworks for actionability, like ESCAT, should be fundamental in developing and implementing NGS-driven, and broadly, precision medicine research and treatments.