BMC Seminar - TP53 mutations in ER-positive breast cancer patients

BMC Seminar Thursday 15 October at 12:00-13:00 in Árnagarður, room 301

Speaker: Snædís Ragnarsdóttir PhD candidate in Stefán Sigurðsson’s lab, Faculty of Medicine, University of Iceland

Title: TP53 mutations predict poor breast cancer-specific survival in ER-positive breast cancer patients

Abstract: TP53 is one of the most frequently mutated genes in breast cancer and plays a central role in maintaining genomic stability by regulating cell cycle progression, DNA repair and apoptosis. Mutations in TP53 are commonly associated with aggressive tumor characteristics and poor clinical outcomes. Although TP53 mutations are considerably more frequent in estrogen receptor-negative (ER-negative) breast cancers, their prognostic impact across different breast cancer subtypes remains incompletely understood.

To investigate this, we analyzed TP53 mutation status and breast cancer-specific survival in a nationwide Icelandic cohort of 1,201 breast cancer patients diagnosed between 1970 and 2003, with long-term clinical follow-up. TP53 mutations were identified through DNA sequencing and their association with survival was evaluated using Kaplan–Meier analyses and multivariable Cox regression models.

Approximately 19% of tumors harbored TP53 mutations, which were associated with significantly poorer breast cancer-specific survival. Interestingly, despite the higher frequency of TP53 mutations in ER-negative tumors, their adverse prognostic association was confined to ER-positive disease. Patients with ER-positive, TP53-mutated tumors had a 2.68-fold increased hazard of breast cancer-specific death, independent of established clinicopathological factors and treatment. In contrast, TP53 mutation status was not independently associated with survival in ER-negative disease. Further analyses suggested that this association may be particularly pronounced in Luminal A tumors, traditionally considered a subtype with favorable prognosis.

These findings reveal a clinically important high-risk subgroup within ER-positive breast cancer and highlight the potential value of TP53 mutation status for improving prognostic stratification.