Genomic Landscape of Small Cell Carcinoma of the Breast (sccb) Contrasted to Small Cell Carcinoma of the Lung (Sclc).

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