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-χ2 = 8.61, P = 0.002) in the NTUH cohort and the PAM50 subtypes (∆ LR-χ2 = 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.

Tumour profiling tests to guide adjuvant chemotherapy decisions in early breast cancer: a systematic review and economic analysis

“…Eleven separate validation cohorts 24,25,58,73,74,77,[122][123][124][125][126][127][128][129] have reported prognostic performance data for IHC4, with a total of 13,434 patients. 127 and the study from Taiwan.…”

“…127 and the study from Taiwan. 124 TransATAC, 46 WSG PlanB, 73,74,77 GEICAM 9906, 129 WSG-AGO-Doc, 123 the Kaiser Permanente cohort, 125 the Institut Curie 128 cohort and the Chinese 58 cohort all recruited or reported a subgroup of HER2-patients. Only one validation cohort (Stephen et al 126 ) treated 100% of patients with endocrine monotherapy, and the remainder treated varying proportions of patients with endocrine therapy and chemotherapy.…”

“…Only one validation cohort (Stephen et al 126 ) treated 100% of patients with endocrine monotherapy, and the remainder treated varying proportions of patients with endocrine therapy and chemotherapy. Two observational studies were from East Asia; 58,124 clinical advice received by the EAG suggests that these two East Asian studies may be less generalisable to the English context because (1) patients were treated in accordance with usual clinical practice and this may differ between these countries and England enough to affect prognostic outcomes and (2) it is possible that people of different ethnicities have different underlying risk profiles and disease natural histories.…”

Detection of somatic TP53 mutation in surgically resected small-cell lung cancer by targeted exome sequencing: association with longer relapse-free survival

“…Wild-type (WT) TP53 in cancer has generally been described as an inducer of cell cycle arrest and apoptosis by cellular stress such as chemotherapy. In many cancer types, a strong correlation exists between the presence of TP53 mutations and reduced responses to chemotherapeutic agents and, thus, a poor prognosis [ 34 , 35 ]. We, therefore, examined whether chemotherapy might be associated with the shorter survival of patients with TP53 mutation than those without in our cohort.…”

Análise da qualidade de vida em mulheres após o diagnóstico de câncer de mama em hospital de referência oncológica no Nordeste brasileiro

“…O câncer de mama é uma das mais relevantes neoplasias em mulheres. Com o surgimento da triagem, um elevado número de pacientes está sendo diagnosticada precocemente e tendo um prognóstico favorável (Lin, 2015).…”