Therapeutic landscape in mutational triple negative breast cancer

Molecular Cancer
Yaqin ShiXiaoxiang Guan

Abstract

Triple negative breast cancer (TNBC) is a heterogeneous disease with aggressive behavior and poor prognosis. Genomic sequencing has detected a distinctive mutational portrait of both the germline and somatic alterations in TNBC, which is staggeringly different from other breast cancer subtypes. The clinical utility of sequencing germline BRCA1/2 genes has been well established in TNBC. However, for other predisposition genes, studies concerning the risk and penetrance to TNBC are relatively scarce. Very few recurrent mutations, including TP53 and PI3KCA mutations, together with a long tail of individually rare mutations occur in TNBC. These combined effects of genomic alterations drive TNBC progression. Given the complexity and heterogeneity of TNBC, clinical interpretation of the genomic alterations in TNBC may pave a new way for the treatment of TNBC. In this review, we summarized the germline and somatic mutation profiles of TNBC and discussed the current and upcoming therapeutic strategies targeting the mutant proteins or pathways to enable tailored-therapeutics.

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Citations

Aug 19, 2020·Veterinary Pathology·Alessandro SammarcoValentina Zappulli
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Methods Mentioned

BETA
genotyping
exome sequencing
xenograft

Clinical Trials Mentioned

NCT01426880
NCT00861705
NCT01905592
NCT01945775
NCT02000622
NCT02203513
NCT01629615
NCT01790932
NCT01623349

Software Mentioned

GeparSixto
Omics

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