探讨在乳腺癌和结直肠癌中检测可干预改变和循环肿瘤DNA的价值

Tumor molecular profiling may reveal distinct biological behaviors by identifying actionable alterations (AAs), informing precision oncology. However, the effect of molecular characteristics on ctDNA detection and monitoring is not well studied. Here, we evaluated patients with breast cancer (BC; all subtypes) or colorectal cancer (CRC) who received whole transcriptome and whole exome profiling with the OncoExTra ® assay and assessment of circulating tumor DNA (ctDNA) status using the Oncodetect™ assay. The primary objective was to describe the frequency of AAs in BC and CRC overall and stratified by ctDNA status, tumor subtype, and clinical stage. In total, 88 patients were evaluated (42 BC and 46 CRC). All CRC patients and 41 BC patients (97.6%) had an AA identified, and 52.3% had an AA associated with FDA-approved therapy. All stage II-IV tumors (80 samples) and 6 of 7 stage I tumors (85.7%) had an AA. HR+/HER2- BC samples had AAs associated with approved matched therapy in 13 (54.2%) samples , which included PIK3CA mutations associated with alpelisib, capivasertib, and/or inavolisib (7 samples; 16.7%) and 1 ESR1 alteration. PIK3CA mutations were present in 9 of 34 (26.5%) stage II/III CRCs, where aspirin therapy has been shown to improve survival. Within our limited cohort, AAs with approved matched therapies were found in 81.8% of stage I-II and 65.7% of stage III-IV CRC and were found in 31.3% and 36.0% of stage I-II vs III-IV BCs, respectively. Among ctDNA-positive BC samples, 27.6% had an AA associated with approved matched therapy vs. 46.2% in ctDNA-negative samples. For CRC, these frequencies were 62.1% and 82.4%, respectively. No association was found between any AA and ctDNA detection. Other AAs associated with FDA-approved therapies are listed in the table. Detection of AAs associated with FDA-approved matched therapy in approximately half of samples tested for ctDNA suggests it may influence therapy selection and disease management.