Ross, Jeffrey S.Badve, SunilWang, KaiSheehan, Christine E.Boguniewicz, Ann B.Otto, Geoff A.Yelensky, RomanLipson, DoronAli, SirajMorosini, DeborahChliemlecki, JuliannElvin, Julia A.Miller, Vincent A.Stephens, Philip J.2015-09-082015-09-082015-05Ross, J. S., Badve, S., Wang, K., Sheehan, C. E., Boguniewicz, A. B., Otto, G. A., ... & Stephens, P. J. (2015). Genomic profiling of advanced-stage, metaplastic breast carcinoma by next-generation sequencing reveals frequent, targetable genomic abnormalities and potential new treatment options. Archives of pathology & laboratory medicine, 139(5), 642.https://hdl.handle.net/1805/6794Context.— Metastatic metaplastic breast carcinoma (MPBC) is an uncommon, but aggressive, tumor resistant to conventional chemotherapy. Objective.— To learn whether next-generation sequencing could identify potential targets of therapy for patients with relapsed and metastatic MPBC. Design.— Hybridization capture of 3769 exons from 236 cancer-related genes and 47 introns of 19 genes commonly rearranged in cancer was applied to a minimum of 50 ng of DNA extracted from 20 MPBC formalin-fixed, paraffin-embedded specimens and sequenced to high uniform coverage. Results.— The 20 patients with MPBC had a median age of 62 years (range, 42–86 years). There were 9 squamous (45%), 9 chondroid (45%), and 2 spindle cell (10%) MPBCs, all of which were high grade. Ninety-three genomic alterations were identified, (range, 1–11) with 19 of the 20 cases (95%) harboring an alteration that could potentially lead to a targeted treatment option. The most-common alterations were in TP53 (n = 69; 75%), PIK3CA (n = 37; 40%), MYC (n = 28; 30%), MLL2 (n = 28; 30%), PTEN (n = 23; 25%), CDKN2A/B (n = 19; 20%), CCND3 (n = 14; 15%), CCNE1 (n = 9; 10%), EGFR (n = 9; 10%), and KDM6A (n = 9; 10%); AKT3, CCND1, CCND2, CDK4, FBXW7, FGFR1, HRAS, NF1, PIK3R1, and SRC were each altered in a single case. All 16 MPBCs (100%) that were negative for ERBB2 (HER2) overexpression by immunohistochemistry and/or ERBB2 (HER2) amplification by fluorescence in situ hybridization were also uniformly (100%) negative for ERBB2 amplification by next-generation sequencing–based copy-number assessment. Conclusions.— Our results indicate that genomic profiling using next-generation sequencing can identify clinically meaningful alterations that have the potential to guide targeted treatment decisions in most patients with metastatic MPBC.en-USIUPUI Open Access Policymetaplastic breast carcinomagenomic profilingArticle