Concordance of Targeted Sequencing from Circulating Tumor DNA and Paired Tumor Tissue for Early Breast Cancer

Purpose: In this study we evaluated the concordance of targeted sequencing between paired circulating tumor DNA (ctDNA) and matched tumor samples from early breast cancers treated with curative intention. Most studies for liquid biopsy were performed for advanced disease, and we reported the scenario of early breast cancer. Materials and Methods The study VGH-TAYLOR comprised a subgroup of early-stage breast cancer. Molecular profiling was performed for both fresh-frozen paraffin-embedded (FFPE) tumor tissue and plasma using the Oncomine Comprehensive Assay v3 and the Oncomine Breast cfDNA Assay v2, respectively. Common genes interrogated by both platforms were identified, and concordance between paired targeted sequencing results from the same individual was reported. Results A total of 612 patients underwent liquid biopsy; 239 (39%) of which reported at least one mutation. Among 246 early-stage patients assayed for both ctDNA and matched tumor, cfDNA assay detected 73 (29.6%) and comprehensive assay detected 201 (81.7%) breast cancers with at least one alteration (c2 test, p = 0.001). Sixty-seven (25.6%) were tested positive for both platforms, while cfDNA and comprehensive assay detected additional 10 (4%) and 138 (56%) cases, respectively. The most prevalent mutant genes were TP53 (68.3%) and KRAS (53.5%), while PIK3CA (39.4%), AKT1 (45.9%) and ERBB2 (17.1%) mutations constituted biomarkers for FDA-approved therapeutics. Conclusion Only one-quarter of breast cancers were concordant between tumor and liquid biopsy from the same subject. Early-stage breast cancer might shed fewer ctDNA from tumor and compromise detectability of liquid biopsy. Our study showed that tumor tissue should be the source of actionable mutation detection for early breast cancers.