Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2025
Erindi/veggspjald / Talk/poster V49
Höfundar / Authors: Snædís Ragnarsdottir, Elísabet Alexandra Frick, Ólafur Andri Stefánsson, Þorkell Guðjónsson, Laufey Tryggvadottir, Linda Vidarsdottir, Stefán Sigurdsson,
Starfsvettvangur / Affiliations: Háskóli Íslands
Kynnir / Presenter: Snædís Ragnarsdóttir
Background: TP53 mutations are frequent in breast cancer (BC) and linked to poor outcomes, but their interaction with estrogen receptor (ER) status and specific chemotherapy regimens needs further investigation. We evaluated whether TP53 mutations predict survival in ER-positive (ER+) patients treated with CMF (cyclophosphamide, methotrexate, 5-fluorouracil) in a nationwide Icelandic cohort with long follow-up. Methods: TP53 status was determined in 1,201 primary breast tumors using Sanger sequencing of exons 5–8, supplemented by whole-genome and targeted deep sequencing in subsets. Clinicopathologic data, ER status and treatments were obtained from the Icelandic Cancer Registry. BC–specific survival was analyzed with Kaplan–Meier and multivariable Cox models accounting for key factors. Results: TP53 mutations were found in 19% of tumors and associated with adverse outcome. Overall, TP53 mutation correlated with worse BC-specific survival. CMF benefited TP53 wild-type patients (HR 0.65, 95% CI 0.43–0.94) but not those with TP53 mutations. In ER+ patients, TP53 mutations predicted poorer outcomes, especially with CMF treatment (HR 4.53, 95% CI 2.38–8.60). Exploratory analyses indicated inferior survival for nonsense/splice-site mutations under CMF. Conclusions: TP53 mutation status is a strong predictor of poor survival in ER+ BC and may identify patients unlikely to benefit from CMF. Incorporating TP53 testing could improve prognostic assessment and guide treatment.