Age- and ethnic-driven molecular and clinical disparity of East Asian breast cancers.

Humans Female Breast Neoplasms / genetics Middle Aged Aged Adult Mutation Age Factors Asian People / genetics Receptor, ErbB-2 / genetics GATA3 Transcription Factor / genetics Aged, 80 and over Class I Phosphatidylinositol 3-Kinases / genetics East Asian People

Breast cancer Ethnic diversity Genomic alterations Molecular subtypes Precision medicine

Journal

BMC medicine

ISSN: 1741-7015

Titre abrégé: BMC Med

Pays: England

ID NLM: 101190723

Informations de publication

Date de publication:
27 Sep 2024

Historique:

received: 05 04 2024

accepted: 13 09 2024

medline: 28 9 2024

pubmed: 28 9 2024

entrez: 28 9 2024

Statut: epublish

Résumé

Breast cancer (BC) is a complex disease with profound genomic aberrations. However, the underlying molecular disparity influenced by age and ethnicity remains elusive. In this study, we aimed to investigate the molecular properties of 843 primary and metastatic BC patients enrolled in the K-MASTER program. By categorizing patients into two distinct age subgroups, we explored their unique molecular properties. Additionally, we leveraged large-scale genomic data from the TCGA and MSK-IMPACT studies to examine the ethnic-driven molecular and clinical disparities. We observed a high prevalence of PI3KCA mutations in K-MASTER HER2 + tumors, particularly in older patients. Moreover, we identified increased mutation rates in DNA damage response molecules, including ARID1A, MSH6, and MLH1. The K-MASTER patients were mainly comprised of triple-negative breast cancer (TNBC) and HER2-positive tumors, while the TCGA and MSK-IMPACT cohorts exhibited a predominance of hormone receptor-positive (HR +) subtype tumors. Importantly, GATA3 mutations were less frequently observed in East Asian patients, which correlated with poor clinical outcomes. In addition to characterizing the molecular disparities, we developed a gradient-boosting multivariable model to identify a new molecular signature that could predict the therapeutic response to platinum-based chemotherapy. Our findings collectively provide unprecedented insights into the significance of age and ethnicity on the molecular and clinical characteristics of BC patients.

Sections du résumé

BACKGROUND BACKGROUND

Breast cancer (BC) is a complex disease with profound genomic aberrations. However, the underlying molecular disparity influenced by age and ethnicity remains elusive.

METHODS METHODS

In this study, we aimed to investigate the molecular properties of 843 primary and metastatic BC patients enrolled in the K-MASTER program. By categorizing patients into two distinct age subgroups, we explored their unique molecular properties. Additionally, we leveraged large-scale genomic data from the TCGA and MSK-IMPACT studies to examine the ethnic-driven molecular and clinical disparities.

RESULTS RESULTS

We observed a high prevalence of PI3KCA mutations in K-MASTER HER2 + tumors, particularly in older patients. Moreover, we identified increased mutation rates in DNA damage response molecules, including ARID1A, MSH6, and MLH1. The K-MASTER patients were mainly comprised of triple-negative breast cancer (TNBC) and HER2-positive tumors, while the TCGA and MSK-IMPACT cohorts exhibited a predominance of hormone receptor-positive (HR +) subtype tumors. Importantly, GATA3 mutations were less frequently observed in East Asian patients, which correlated with poor clinical outcomes. In addition to characterizing the molecular disparities, we developed a gradient-boosting multivariable model to identify a new molecular signature that could predict the therapeutic response to platinum-based chemotherapy.

CONCLUSIONS CONCLUSIONS

Our findings collectively provide unprecedented insights into the significance of age and ethnicity on the molecular and clinical characteristics of BC patients.

Identifiants

DOI: 10.1186/s12916-024-03638-y PMID: 39334392

pubmed: 39334392

doi: 10.1186/s12916-024-03638-y

pii: 10.1186/s12916-024-03638-y

doi:

Substances chimiques

Receptor, ErbB-2 EC 2.7.10.1

GATA3 Transcription Factor 0

ERBB2 protein, human EC 2.7.10.1

GATA3 protein, human 0

Class I Phosphatidylinositol 3-Kinases EC 2.7.1.137

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

422

Subventions

Organisme : National Research Foundation of Korea

ID : RS-2023-00209742

Organisme : Ministry of Health and Welfare

ID : HI17C2206

Informations de copyright

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