TP53 Germline Mutation Testing in Early-onset Breast Cancer: Findings from a Nationwide Cohort

Overview

Journal Fam Cancer

Publisher Springer

Specialty Oncology

Date 2019 Jan 5

PMID 30607672

Citations 17

Authors

J J Bakhuizen

F B Hogervorst

M E Velthuizen

M W Ruijs

K van Engelen

T A van Os

J J Gille

M Collee

A M van den Ouweland

C J van Asperen

C M Kets

A R Mensenkamp

E M Leter

M J Blok

M M de Jong

M G Ausems

Affiliations

Soon will be listed here.

Abstract

Early-onset breast cancer may be due to Li-Fraumeni Syndrome (LFS). Current national and international guidelines recommend that TP53 genetic testing should be considered for women with breast cancer diagnosed before the age of 31 years. However, large studies investigating TP53 mutation prevalence in this population are scarce. We collected nationwide laboratory records for all young breast cancer patients tested for TP53 mutations in the Netherlands. Between 2005 and 2016, 370 women diagnosed with breast cancer younger than 30 years of age were tested for TP53 germline mutations, and eight (2.2%) were found to carry a (likely) pathogenic TP53 sequence variant. Among BRCA1/BRCA2 mutation negative women without a family history suggestive of LFS or a personal history of multiple LFS-related tumours, the TP53 mutation frequency was < 1% (2/233). Taking into consideration that TP53 mutation prevalence was comparable or even higher in some studies selecting patients with breast cancer onset at older ages or HER2-positive breast cancers, raises the question of whether a very early age of onset is an appropriate single TP53 genetic testing criterion.

Citing Articles

Germline Variant Spectrum in Southern Italian High-Risk Hereditary Breast Cancer Patients: Insights from Multi-Gene Panel Testing.

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Case series of Li-Fraumeni syndrome: carcinogenic mechanisms in breast cancer with TP53 pathogenic variant carriers.

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Pedigree analysis exploring the inconsistency between diverse phenotypes and testing criteria for germline TP53 mutations in Chinese women with breast cancer.

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Overview of the Genetic Causes of Hereditary Breast and Ovarian Cancer Syndrome in a Large French Patient Cohort.

Bouras A, Guidara S, Leone M, Buisson A, Martin-Denavit T, Dussart S Cancers (Basel). 2023; 15(13).

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Emerging insights into ethnic-specific TP53 germline variants.

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