Abstract A32: MCL1 gene amplification in breast cancer is associated with TNBC status and can respond to a sorafenib/vorinostat regimen

Background: MCL1 encodes the induced myeloid leukemia cell differentiation protein Mcl-1, a member of the BCL-2 family which functions to inhibit apoptosis. Mcl-1 over-expression has been associated with high tumor grade and adverse prognosis in triple negative breast cancer (TNBC) but therapies specifically leading to inhibition of MCL-1 have not been identified. Methods: Comprehensive genomic profiling (CGP) using hybridization capture of 3,769 exons from 315 cancer-related genes and 47 introns of 19 genes commonly rearranged in cancer was applied to ≥50ng of DNA extracted from 2,824 consecutive BC and sequenced to high, uniform median coverage (>600X). The original primary BC was assayed in 44% of cases and a sample from a metastatic focus was assayed in 56% of cases. Results: Of 2824 consecutive BC cases, 200 (7.1%) cases harbored MCL1 amplification. Of these MCL1-amplified cases, 146 (73%) were TNBC and 54 were non-TNBC (p