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Background: SCCBis a rare, aggressive form of breast cancer that is associated ith extremely poor outcomes Hare 2015 . In an effort to identify ne treatment options, e utilized comprehensive genomic profiling to assess the potential for novel therapies in SCCB. Methods: Under an IRB approved protocol, e identified patients pts ith SCCB and SCLC profiled by Caris Life Sciences beteen 2007-2015. Tumors ere assessed ith up to 21 IHC stains, in situ hybridization ISH of cMET, EGFR, HER2 and TOP2A, and next generation sequencing NGS as ell as Sanger sequencing of 47 genes. Results: 19 patients ith SCCB ere identified, median age as 58 years range 37-79 and 42 percent had metastatic disease at presentation; for comparison 58 pts ith SCLC ere identified 66 [36-86], 65 percent metastatic . By IHC 30 percent SCCB pts expressed ER, 15 percent expressed PR and 18 percent expressed androgen receptor; SCLC pts expressed ER 0 percent, PR 2 percent, AR 6 percent. SCCB and SCLC pts had similar patterns of other IHC expression 0 percent v 0 percent PDL1, 50 percent v 42 percent PD1, 80 percent v 95 percent TOP2A, respectively . All SCCB and SCLC pts ere negative for HER2 and cMET amplification by ISH. NGS revealed TP53 mutations in 75 percent of patients both ith SCCB and SCLC and PIK3CA mutations in 38 percent of SCCB pts but no SCLC pts Fishers exact test p = 0.005, OR 0.02 [0.00-0.52] . No other mutations ere found in SCCB pts and no other mutation occurred in over 10 percent of SCLC pts except RB1 in 20 percent p = 0.31 . Conclusions: SCCB is an aggressive tumor ith fe therapeutic options. Molecular profiling suggests many similarities beteen SCCB and SCLC ith the exception an increased incidence of PIK3CA mutations in SCCB, hich may have therapeutic implications.,J Clin Oncol 34, 2016 suppl; abstr e23281 ,Publication Only Tumor Biology

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