Background: TheTP53mutation 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 ofTP53mutations across all breast cancer subtypes and treatments utilizing long-term follow-up data. Methods: We retrospectively identified the data of breast cancer patients who underwentTP53mutation testing. Stratified log-rank tests and Cox regression analysis were performed to compare oncologic outcomes based onTP53mutation 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 underwentTP53mutation testing in Gangnam Severance Hospital. TheTP53mutations were identified in 172 patients (26.5%), with 34 (19.8%) exhibiting missense hotspot mutations. Patients withTP53mutations (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 theTP53-mutated group did not reveal significant differences in oncologic outcomes based on mutation types and locations. Conclusions: Our findings establish thatTP53mutations are linked to poorer oncologic outcomes in breast cancer across all subtypes. Yet, within theTP53-mutated group, the specific characteristics ofTP53mutations do not influence oncologic outcomes.
背景：TP53突变是人类癌症中最常见的突变之一，通常与不良预后相关。然而，关于其影响的研究结果存在矛盾。本研究旨在利用长期随访数据，阐明TP53突变在所有乳腺癌亚型及治疗中的临床相关性。方法：我们回顾性分析了接受TP53突变检测的乳腺癌患者数据。采用分层对数秩检验和Cox回归分析，比较基于TP53突变状态及其特征（包括突变类型和位置）的肿瘤学结局。使用聚合酶链反应-变性高效液相色谱法（PCR-DHPLC）和直接测序技术检测第5-9外显子的突变。结果：2007年1月至2015年12月期间，江南Severance医院共有650例乳腺癌患者接受了TP53突变检测。其中172例（26.5%）检出TP53突变，34例（19.8%）存在错义热点突变。TP53突变组患者预后较差，其10年无复发生存率为83.5%，而未突变组为86.6%（风险比1.67；p=0.026）；10年总生存率分别为88.1%和91.0%（风险比3.02；p=0.003）。然而，在TP53突变组内进行的亚组分析显示，基于突变类型和位置的肿瘤学结局无显著差异。结论：本研究证实TP53突变与所有亚型乳腺癌较差的肿瘤学结局相关。但在TP53突变组内，TP53突变的具体特征并不影响肿瘤学结局。
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