Show simple item record

AuthorSemir, Vranic
AuthorStafford, Phillip
AuthorPalazzo, Juan
AuthorSkenderi, Faruk
AuthorSwensen, Jeffrey
AuthorXiu, Joanne
AuthorSpetzler, David
AuthorGatalica, Zoran
Available date2020-03-08T04:51:00Z
Publication Date2020-02-27
Publication NameClinical Breast Canceren_US
Identifierhttp://dx.doi.org/10.1016/j.clbc.2020.02.008
CitationVranic S, Stafford P, Palazzo J, Skenderi F, Swensen J, Xiu J, Spetzler D, Gatalica Z, Molecular profiling of the metaplastic spindle cell carcinoma of the breast reveals potentially targetable biomarkers, Clinical Breast Cancer (2020), doi: https://doi.org/10.1016/j.clbc.2020.02.008.
ISSN1526-8209
URIhttps://www.sciencedirect.com/science/article/pii/S1526820920300434?v=s5
URIhttp://hdl.handle.net/10576/13273
AbstractIntroductionSpindle cell carcinoma is a rare subtype of metaplastic breast cancer (MBC), with triple-negative (TNBC: ER-/PR-/Her2-) phenotype. It is associated with a marked resistance to conventional chemotherapy and has overall poor outcome. Materials and MethodsTwenty-three pure spindle cell carcinomas of the breast (18 primary and 5 recurrent/metastatic) were comprehensively explored for biomarkers of immuno-oncology (I-O) and targeted therapies using immunohistochemistry and DNA/RNA sequencing. ResultsThe majority (21/23) of spindle cell carcinomas were TNBC. Estrogen and androgen receptors expression above the therapeutic thresholds were detected in two cases, each. Pathogenic gene mutations were identified in 21/23 cases including PIK3CA, TP53, HRAS, NF1, and PTEN. One case with matched pre- and post-chemotherapy samples exhibited a consistent mutational profile (PIK3CA and HRAS mutations) in both samples. Gene amplifications were present in five cases including one case without detectable mutations. The spindle cell carcinomas cohort had consistently low total mutational burden (all below 80th percentile for the entire TNBC cohort). All tumors were microsatellite stable. PD-L1 expression was observed on both tumor cells (TC, in 7/21 cases), and in tumor infiltrating immune cells (IC, 2/21 cases). ConclusionsSpindle cell carcinomas are characterized by targetable molecular alterations in the majority of cases, but due to the lack of uniform findings, individual patient profiling is necessary. Detection of individual combinations of biomarkers should improve treatment options for this rare, but aggressive disease.
Languageen
PublisherElsevier
SubjectBreast cancer
Subjectmetaplastic carcinoma
Subjectspindle cell carcinoma
Subjectmolecular profiling
Subjectimmune checkpoint inhibitors
Subjecttargeted therapy
Subjectmutations
TitleMolecular profiling of the metaplastic spindle cell carcinoma of the breast reveals potentially targetable biomarkers
TypeArticle
Open Access user License http://creativecommons.org/licenses/by-nc-nd/4.0/


Files in this item

Icon

This item appears in the following Collection(s)

Show simple item record