Genome wide copy number analysis of chemotherapy resistant metastatic triple negative breast cancer from cell free DNA

1092Background: Triple-negative breast cancer (TNBC) is a poor prognosis breast cancer subset characterized by relatively few mutations but extensive copy number alterations (CNAs). Cell-free DNA (cfDNA) offers the potential to overcome infrequent tumor biopsies in metastatic TNBC (mTNBC) and interrogate the genomics of chemotherapy resistance. Methods: 506 archival or fresh plasma samples were identified from 164 patients with mTNBC who had previously received chemotherapy. We performed low coverage sequencing to determine genome-wide copy number and estimate ‘tumor fraction’ of cfDNA (TFx). In patient samples with TFx u003e10%, we identified regions that were significantly gained or lost using GISTIC2.0. We compared CNAs of mTNBCs with primary TNBCs from a publicly-available dataset, METABRIC (TNBC n=277). Results: We successfully obtained high quality, low coverage whole genome sequencing data for 478 (94.5%) plasma samples from 158 patients, with 1 to 14 samples per patient. Archival samples had significa...