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Concomitant PIK3CA and TP53 Mutations in Breast Cancer: An Analysis of Clinicopathologic and Mutational Features, Neoadjuvant Therapeutic Response, and Prognosis

PURPOSE: PIK3CA and TP53 are the most prevalently mutated genes in breast cancer (BC). Previous studies have indicated an association between concomitant PIK3CA/TP53 mutations and shorter disease-free survival. As its clinical utility remains largely unknown, we aimed to analyze the prognostic and p...

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Autores principales: Lin, Xiao-Yi, Guo, Lijuan, Lin, Xin, Wang, Yulei, Zhang, Guochun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Breast Cancer Society 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10475711/
https://www.ncbi.nlm.nih.gov/pubmed/37565929
http://dx.doi.org/10.4048/jbc.2023.26.e30
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author Lin, Xiao-Yi
Guo, Lijuan
Lin, Xin
Wang, Yulei
Zhang, Guochun
author_facet Lin, Xiao-Yi
Guo, Lijuan
Lin, Xin
Wang, Yulei
Zhang, Guochun
author_sort Lin, Xiao-Yi
collection PubMed
description PURPOSE: PIK3CA and TP53 are the most prevalently mutated genes in breast cancer (BC). Previous studies have indicated an association between concomitant PIK3CA/TP53 mutations and shorter disease-free survival. As its clinical utility remains largely unknown, we aimed to analyze the prognostic and predictive roles of this co-mutation. METHODS: We retrospectively analyzed patients who were diagnosed with BC at Guangdong Provincial People’s Hospital (GDPH) who underwent next-generation sequencing. The correlation of concomitant PIK3CA/TP53 mutations with clinicopathological and mutational characteristics, and neoadjuvant systemic therapy (NST) responses was analyzed. The Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset was used to verify associations between concurrent mutations and survival outcomes. RESULTS: In the GDPH cohort, concomitant PIK3CA/TP53 mutations were associated with more aggressive phenotypes, including human epidermal growth factor receptor 2 positive status, hormone receptor negative status, high Ki-67 expression, high histological grade, advanced TNM stage, and additional genetic alterations. Co-mutations also portended a worse response to NST, especially taxane-containing regimens, when compared with the TP53 mutant alone (odds ratio, 3.767; 95% confidence interval, 1.205–13.087; p = 0.028). A significant association was observed between concomitant PIK3CA/TP53 mutations and poor survival outcomes in the METABRIC cohort. CONCLUSION: Concomitant PIK3CA/TP53 mutations not only suggested unfavorable features and poor prognosis in BC but also conferred less benefit to NST than TP53 mutations alone.
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spelling pubmed-104757112023-09-05 Concomitant PIK3CA and TP53 Mutations in Breast Cancer: An Analysis of Clinicopathologic and Mutational Features, Neoadjuvant Therapeutic Response, and Prognosis Lin, Xiao-Yi Guo, Lijuan Lin, Xin Wang, Yulei Zhang, Guochun J Breast Cancer Original Article PURPOSE: PIK3CA and TP53 are the most prevalently mutated genes in breast cancer (BC). Previous studies have indicated an association between concomitant PIK3CA/TP53 mutations and shorter disease-free survival. As its clinical utility remains largely unknown, we aimed to analyze the prognostic and predictive roles of this co-mutation. METHODS: We retrospectively analyzed patients who were diagnosed with BC at Guangdong Provincial People’s Hospital (GDPH) who underwent next-generation sequencing. The correlation of concomitant PIK3CA/TP53 mutations with clinicopathological and mutational characteristics, and neoadjuvant systemic therapy (NST) responses was analyzed. The Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset was used to verify associations between concurrent mutations and survival outcomes. RESULTS: In the GDPH cohort, concomitant PIK3CA/TP53 mutations were associated with more aggressive phenotypes, including human epidermal growth factor receptor 2 positive status, hormone receptor negative status, high Ki-67 expression, high histological grade, advanced TNM stage, and additional genetic alterations. Co-mutations also portended a worse response to NST, especially taxane-containing regimens, when compared with the TP53 mutant alone (odds ratio, 3.767; 95% confidence interval, 1.205–13.087; p = 0.028). A significant association was observed between concomitant PIK3CA/TP53 mutations and poor survival outcomes in the METABRIC cohort. CONCLUSION: Concomitant PIK3CA/TP53 mutations not only suggested unfavorable features and poor prognosis in BC but also conferred less benefit to NST than TP53 mutations alone. Korean Breast Cancer Society 2023-07-12 /pmc/articles/PMC10475711/ /pubmed/37565929 http://dx.doi.org/10.4048/jbc.2023.26.e30 Text en © 2023 Korean Breast Cancer Society https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Lin, Xiao-Yi
Guo, Lijuan
Lin, Xin
Wang, Yulei
Zhang, Guochun
Concomitant PIK3CA and TP53 Mutations in Breast Cancer: An Analysis of Clinicopathologic and Mutational Features, Neoadjuvant Therapeutic Response, and Prognosis
title Concomitant PIK3CA and TP53 Mutations in Breast Cancer: An Analysis of Clinicopathologic and Mutational Features, Neoadjuvant Therapeutic Response, and Prognosis
title_full Concomitant PIK3CA and TP53 Mutations in Breast Cancer: An Analysis of Clinicopathologic and Mutational Features, Neoadjuvant Therapeutic Response, and Prognosis
title_fullStr Concomitant PIK3CA and TP53 Mutations in Breast Cancer: An Analysis of Clinicopathologic and Mutational Features, Neoadjuvant Therapeutic Response, and Prognosis
title_full_unstemmed Concomitant PIK3CA and TP53 Mutations in Breast Cancer: An Analysis of Clinicopathologic and Mutational Features, Neoadjuvant Therapeutic Response, and Prognosis
title_short Concomitant PIK3CA and TP53 Mutations in Breast Cancer: An Analysis of Clinicopathologic and Mutational Features, Neoadjuvant Therapeutic Response, and Prognosis
title_sort concomitant pik3ca and tp53 mutations in breast cancer: an analysis of clinicopathologic and mutational features, neoadjuvant therapeutic response, and prognosis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10475711/
https://www.ncbi.nlm.nih.gov/pubmed/37565929
http://dx.doi.org/10.4048/jbc.2023.26.e30
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