alexa Genomic and protein alterations in 126 triple-negative (TN) metaplastic breast cancers.


Journal of Carcinogenesis & Mutagenesis

Author(s): Feldman RA, Millis SZ

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Background: Metaplastic breast cancer (MpBC) is a rare subtype (less than 1% of all breast cancers), is generally ER, PR and HER2-negative (TN), demonstrates a claudin-low gene expression profile, and is poorly responsive to cytotoxic therapy. Little is known about the genomic alterations (GA) in MpBC nor about overexpressed proteins that may be amenable to targeted therapy. Methods: Of 2000 TN breast cancers (TNBC) referred to Caris Life Sciences since 2009 from 50 states and 59 countries, 126 cases were TN MpBCs based on local pathology evaluation. Specific testing was performed per physician request and included sequencing (Sanger or next generation sequencing [NGS]), protein expression (immunohistochemistry [IHC]), and/or gene amplification (CISH or FISH). Results: The Table shows the percent gene mutations, amplifications, and IHC findings for biomarkers that were different between TNBC and MpBCs, as a percentage of total patients tested. Conclusions: Comparison of the genomic and protein expression profiles highlights some differences between the two cancers.Multiplatform profiling shows that most MpBCs have gene alterations in the PI3K pathway. The low RRM1 expression rate suggests possible gemcitabine effectiveness. Other potential therapeutically targetable gene alterations are present at low incidence in this large series of MpBCs.

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This article was published in J Clin Oncol and referenced in Journal of Carcinogenesis & Mutagenesis

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