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  11. Breast Cancer Plasticity After Chemotherapy Highlights The Need For Re-evaluation Of Subtyping In Residual Cancer And Metastatic Tissues

Breast Cancer Plasticity after Chemotherapy Highlights the Need for Re-Evaluation of Subtyping in Residual Cancer and Metastatic Tissues

Irena Barbara Padzińska-Pruszyńska1, Muhammad Waqas Akbar2, Murat Isbilen3

  • 1Center of Cellular Immunotherapies, Warsaw University of Life Sciences, 02-786 Warsaw, Poland.

International Journal of Molecular Sciences
|June 19, 2024

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View abstract on PubMed

Summary
This summary is machine-generated.

Novel biomarkers can predict outcomes for triple-negative breast cancer (TNBC) patients undergoing neoadjuvant therapy. Gene expression analysis reveals that low Wingless/Integrated-pathway and mesenchymal (Wnt/Mes) marker expression correlates with better survival in TNBC.

Area of Science:

  • Oncology
  • Genomics
Keywords:
PAM50 plasticityTNBCWNT/Mesbreast cancer

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  • Molecular Biology

    • Background:

    • Triple-negative breast cancer (TNBC) presents a significant clinical challenge, particularly for patients receiving neoadjuvant therapy.
    • Identifying reliable prognostic biomarkers is crucial for tailoring treatment strategies and improving patient outcomes.
    • Understanding the molecular mechanisms underlying treatment response and resistance in TNBC is an unmet need.

    Purpose of the Study:

    • To identify novel gene expression biomarkers for prognostication in TNBC patients eligible for neoadjuvant therapy.
    • To investigate the dynamic changes in tumor molecular subtypes following chemotherapy and their impact on therapeutic efficacy.
    • To explore the potential of molecular subtyping for refining treatment strategies in relapsed or metastatic TNBC.

    Main Methods:

    • Survival and RNA sequencing data from a cohort of TNBC patients were analyzed.
    • Gene expression data were used to classify patients based on Wingless/Integrated-pathway (Wnt-pathway) and mesenchymal (Mes) markers (Wnt/Mes).
    • In silico analysis using Prediction Analysis of Microarray 50 (PAM50) was performed to classify tumor subtypes before and after treatment.

    Main Results:

    • A list of 276 genes related to survival in TNBC patients was identified.
    • Low Wnt/Mes gene expression was associated with favorable outcomes (no deaths), while high expression correlated with a 50% mortality rate within 19 months.
    • Significant shifts in gene expression profiles were observed post-chemotherapy, with tumors often transitioning to a more mesenchymal/stem cell-like profile, potentially reducing therapeutic efficacy.

    Conclusions:

    • The identified Wnt/Mes gene signature serves as a potential prognostic biomarker for TNBC patients undergoing neoadjuvant therapy.
    • Tumor molecular subtyping can dynamically change post-chemotherapy, leading to treatment resistance and necessitating reevaluation.
    • Personalized treatment strategies based on dynamic molecular subtyping are essential for optimizing outcomes in TNBC, especially in cases of relapse or metastasis.
    prognostic markers