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Clinical Relevance of TP53 Mutation and Its Characteristics in Breast Cancer with Long-Term Follow-Up Date
by
, , , and
Seung Hyun Hwang
1,2, 
Seung Ho Baek
1,3,
Min Ji Lee
1,3,
Yoonwon Kook
1,3,
Soong June Bae
1,3,
Sung Gwe Ahn
1,3 and
Joon Jeong
1,3,* 1
Institute for Breast Cancer Precision Medicine, Yonsei University College of Medicine, Seoul 06273, Republic of Korea
2
Department of Breast and Thyroid Surgery, Sam Hospital, Anyang 14030, Republic of Korea
3
Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea
*
Author to whom correspondence should be addressed.
Cancers 2024, 16(23), 3899; https://doi.org/10.3390/cancers16233899
Submission received: 25 September 2024
/
Revised: 30 October 2024
/
Accepted: 30 October 2024
/
Published: 21 November 2024
(This article belongs to the Section Clinical Research of Cancer)
Simple Summary
The TP53 mutation is one of the prevalent genetic alterations in human cancers and is often linked to a poor prognosis. While earlier studies have produced mixed results, they frequently involved small patient groups focused on specific breast cancer subtypes and treatments. To clarify these findings, we examined the clinical relevance of TP53 mutations in 650 patients across all subtypes, with consistent treatment based on subtype. In total, 172 (26.5%) had TP53 mutations, including 34 (19.8%) with missense hotspot mutations. Those with TP53 mutations had worse outcomes, with a 10-year recurrence-free survival rate of 83.5% compared to 86.6% for those without (p = 0.026), and a 10-year overall survival rate of 88.1% versus 91.0% (p = 0.003). However, the outcomes among patients with TP53 mutation did not differ significantly by mutation types or locations. Consequently, further research is necessary to explore the clinical relevance of the characteristics of TP53 mutation.
Abstract
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.
