TP53 Mutational Analysis Enhances the Prognostic Accuracy of IHC4 and PAM50 Assays.

Abstract:

:IHC4 and PAM50 assays have been shown to provide additional prognostic information for patients with early breast cancer. We evaluated whether incorporating TP53 mutation analysis can further enhance their prognostic accuracy. We examined TP53 mutation and the IHC4 score in tumors of 605 patients diagnosed with stage I-III breast cancer at National Taiwan University Hospital (the NTUH cohort). We obtained information regarding TP53 mutation and PAM50 subtypes in 699 tumors from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort. We found that TP53 mutation was significantly associated with high-risk IHC4 group and with luminal B, HER2-enriched, and basal-like subtypes. Despite the strong associations, TP53 mutation independently predicted shorter relapse-free survival (hazard ratio [HR] = 1.63, P = 0.007) in the NTUH cohort and shorter breast cancer-specific survival (HR = 2.35, P = <0.001) in the METABRIC cohort. TP53 mutational analysis added significant prognostic information in addition to the IHC4 score (∆ LR-χ(2) = 8.61, P = 0.002) in the NTUH cohort and the PAM50 subtypes (∆ LR-χ(2) = 18.9, P = <0.001) in the METABRIC cohort. We conclude that incorporating TP53 mutation analysis can enhance the prognostic accuracy of the IHC4 and PAM50 assays.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Lin CH,Chen IC,Huang CS,Hu FC,Kuo WH,Kuo KT,Wang CC,Wu PF,Chang DY,Wang MY,Chang CH,Chen WW,Lu YS,Cheng AL

doi

10.1038/srep17879

subject

Has Abstract

pub_date

2015-12-16 00:00:00

pages

17879

issn

2045-2322

pii

srep17879

journal_volume

5

pub_type

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