Liquid Biopsy Detects Relapse Five Months Earlier thanRegular Clinical Follow-Up and Guides Targeted Treatment inBreast Cancer

Genetic alterations in circulating tumor DNA (ctDNA) are an emerging biomarker for the early detection of relapse and have thepotential to guide targeted treatment. ctDNA analysis is often performed by droplet digital PCR; however, next-generationsequencing (NGS) allows multigene testing without having to access a tumor sample to identify target alterations. Here, wereport the case of a stage III hormone receptor-positive breast cancer patient who remained symptomless after receivingsurgery and adjuvant chemotherapy. Liquid biopsy analysis by NGS revealed the presence of a ctDNAPIK3CAN345Kmutationfive months before the detection of relapse with multiple liver metastases by regular clinical follow-up. To date,clinical implications of thePIK3CAN345K variant remain insufficiently investigated; however, everolimus treatment resultedin the shrinkage of tumor lesions and decreased the levels of tumor markers. Four months after treatment initiation, a secondctDNA analysis suggested a relapse, and the patient clinically progressed afterfive months of everolimus therapy. This casereport demonstrates the value of ctDNA analysis by NGS for the early detection of relapse in breast cancer patients. The studyfurther indicates its usefulness for the choice of targeted treatments, suggesting that the variantPIK3CAN345K might beassociated with everolimus sensitivity.