Clinical Relevance of TP53 Mutation and Its Characteristics in Breast Cancer with Long-Term Follow-Up Date

Background: The TP53 mutation is one of the most frequently identified mutations in human cancers and is typically associated with a poor prognosis. However, there are conflicting findings regarding its impact. We aimed to clarify the clinical relevance of TP53 mutations across all breast cancer subtypes and treatments utilizing long-term follow-up data. Methods: We retrospectively identified the data of breast cancer patients who underwent TP53 mutation testing. Stratified log-rank tests and Cox regression analysis were performed to compare oncologic outcomes based on TP53 mutation status and the characteristics of these mutations, including types and locations. Mutations in exons 5-9 were identified using polymerase chain reaction-denaturing high-performance liquid chromatography (PCR-DHPLC) and direct sequencing. Results: Between January 2007 and December 2015, 650 breast cancer patients underwent TP53 mutation testing in Gangnam Severance Hospital. The TP53 mutations were identified in 172 patients (26.5%), with 34 (19.8%) exhibiting missense hotspot mutations. Patients with TP53 mutations (TP53-mutated group) had worse prognosis, demonstrated by a 10-year recurrence-free survival (RFS) rate of 83.5% compared to 86.6% in patients without mutations (HR, 1.67; p = 0.026) and a 10-year overall survival (OS) rate of 88.1% versus 91.0% (HR, 3.02; p = 0.003). However, subgroup analyses within the TP53-mutated group did not reveal significant differences in oncologic outcomes based on mutation types and locations. Conclusions: Our findings establish that TP53 mutations are linked to poorer oncologic outcomes in breast cancer across all subtypes. Yet, within the TP53-mutated group, the specific characteristics of TP53 mutations do not influence oncologic outcomes.