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Arch Pathol Lab Med. 2015 May;139(5):642-9. doi: 10.5858/arpa.2014-0200-OA.

Genomic profiling of advanced-stage, metaplastic breast carcinoma by next-generation sequencing reveals frequent, targetable genomic abnormalities and potential new treatment options.

Author information

1
From the Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York (Drs Ross and Boguniewicz and Ms Sheehan); Research and Development, Foundation Medicine, Inc, Cambridge, Massachusetts (Drs Ross, Wang, Otto, Yelensky, Lipson, Ali, Morosini, Chliemlecki, Elvin, Miller, and Stephens); and the Department of Pathology, University of Indiana School of Medicine, Indianapolis (Dr Badve).

Abstract

CONTEXT:

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.

PMID:
25927147
DOI:
10.5858/arpa.2014-0200-OA
[Indexed for MEDLINE]
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