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.