title: 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.
authors.affiliation: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.|Department of Internal Medicine; National Taiwan University Hospital, Taipei, Taiwan.|Oncology Center, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan.
authors.forename: Ching-Hung
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: I-Chiun
authors.initials: IC
authors.lastname: Chen
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chiun-Sheng
authors.initials: CS
authors.lastname: Huang
authors.affiliation: Graduate Institute of Clinical Medicine and School of Nursing, College of Medicine, National Taiwan University, Taipei, Taiwan.|International-Harvard Statistical Consulting Company, Taipei, Taiwan.
authors.forename: Fu-Chang
authors.initials: FC
authors.lastname: Hu
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Wen-Hung
authors.initials: WH
authors.lastname: Kuo
authors.affiliation: Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Kuan-Ting
authors.initials: KT
authors.lastname: Kuo
authors.affiliation: Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chung-Chieh
authors.initials: CC
authors.lastname: Wang
authors.affiliation: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Pei-Fang
authors.initials: PF
authors.lastname: Wu
authors.affiliation: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Dwan-Ying
authors.initials: DY
authors.lastname: Chang
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Ming-Yang
authors.initials: MY
authors.lastname: Wang
authors.affiliation: Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chin-Hao
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Wei-Wu
authors.initials: WW
authors.lastname: Chen
authors.affiliation: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.|Department of Internal Medicine; National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Yen-Shen
authors.initials: YS
authors.lastname: Lu
authors.affiliation: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.|Department of Internal Medicine; National Taiwan University Hospital, Taipei, Taiwan.|Graduate Institute of Oncology and Cancer Research Centre, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Ann-Lii
authors.initials: AL
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D013624:Taiwan; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53