Serial genomic analysis of circulating tumor cells and circulating tumor DNA in triple-negative and HER2-positive advanced, metastatic breast cancer.

Abstract

e12561 Background: Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) have a promising role for detecting early response and progression in breast cancer. We performed serial genomic analysis of CTC and ctDNA in advanced, metastatic triple negative breast cancer (TNBC) and HER2 positive breast cancer (BC). Methods: Serial CTCs, ctDNA were prospectively collected in 9 early or advanced, and 10 metastatic BC patients periodically during systemic chemotherapy. CTC was isolated from whole blood through EpCAM positive bead selection, and ctDNA was isolated from plasma. For genomic profiling of CTC and ctDNA, Oncomine™ Comprehensive Assay Plus and Oncomine™ Pan-Cancer cfDNA assay (included BRCA1, BRCA2 and MYCN customized panel) was performed and analyzed, respectively. Results: TP63 was most commonly detected mutation (13 patients, 68.4%) at serial CTC analysis with median variant of allele frequency (VAF) of 18.6% (range 11.5̃25.2%), irrespective of tumor subtype and stage. In ctDNA analysis, 11 patients showed TP53 mutation with low VAF (median 1.4%, range 0.3̃12.3%). FGFR4 was equally detected, with median variant of allele frequency (VAF) of 57.2% (range 46.6-99.8) and there was no change of FGFR4 VAF irrespective of tumor response in CTC analysis. In three gBRCA1 mutated patients, BRCA1 was identically detected in 3 patients based on CTC analysis and in 2 patients based on ctDNA analysis with VAF of approximately 50%. There were no significant changes of VAF in target mutations of CTC irrespective of tumor response and subtype. In TNBC patients who received neoadjuvant chemotherapy, tumor mutation burden (TMB) showed gradual decrease during treatment. However, there were initial surge of TMB in HER2 positive BC patients who received neoadjuvant chemotherapy, irrespective of presence of pathologic complete response. Conclusions: Our study suggest that serial follow up CTC and ctDNA is feasible and reflect the general characteristics of baseline characteristics and dynamic molecular alteration of breast cancer. Further analysis with larger patient sample and correlation with tumor tissue is warranted in the future.