Actionable Alterations and ctDNA Testing Refine Precision Strategies in Breast and Colorectal Cancers

Actionable Alterations and ctDNA Testing May Refine Precision Strategies in Breast and Colorectal Cancers Molecular testing identified actionable alterations in high proportions of patients with breast and colorectal cancers, regardless of ctDNA status. Comprehensive genomic profiling of both tumor tissue and circulating tumor DNA (ctDNA) enables detection of therapeutically relevant variants that guide targeted therapy decisions. Liquid biopsy approaches, particularly ctDNA analysis, are emerging as sensitive and reliable surrogates for tumor tissue-based routine diagnostic testing in oncology. In non-small cell lung cancer (NSCLC) patients, ctDNA analysis demonstrated comparable detection rates of actionable mutations to tissue-based next-generation sequencing (NGS). In a retrospective study of 180 plasma samples from NSCLC patients, mutations were concordantly detected in tumor tissue and plasma in 82% of cases. While tissue-based NGS identified more mutations in 19 patients, plasma testing revealed additional mutations in four patients. Molecular tumor profiling identified 60 patients eligible for targeted treatment, including 15 (8%) harboring fusions not covered by the UltraSEEK Lung Panel v2. Based on ctDNA analysis, 41 patients (23%) were identified as eligible for BRAFV600-, EGFR-, or KRASG12C-targeted therapies. In the absence of tumor tissue NGS data for 48 patients, five therapeutically relevant mutations were detected through ctDNA testing alone. These findings support the clinical utility of ctDNA testing as an alternative or complementary method for detecting actionable genomic alterations when tissue sampling is limited or unavailable. The ability to identify therapeutically relevant variants through liquid biopsy expands access to precision medicine approaches, particularly for patients who cannot undergo invasive tissue biopsies. Serial monitoring of ctDNA similarly enables real-time assessment of treatment response and early detection of resistance mechanisms, further refining therapeutic strategies in breast and colorectal cancers. As liquid biopsy technologies continue to advance, their integration into routine clinical practice holds promise for improving patient outcomes through more personalized and timely interventions.