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Exploration of the clonal evolution and construction of the tumor clonal evolution rate as a prognostic indicator in

Dan Lv1, Bo Lan1, Qihan Guo2

  • 1Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

BMC Medicine
|February 26, 2025
PubMed
Summary
This summary is machine-generated.

Metastatic breast cancer (MBC) clonal evolution patterns, particularly branched evolution, are linked to better treatment outcomes. A novel indicator, tumor clonal evolution rate (TER), derived from circulating tumor DNA (ctDNA), can predict prognosis.

Keywords:
Breast cancerCirculating tumor DNAClonal evolutionTumor evolution rate

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Area of Science:

  • Oncology
  • Genomics
  • Molecular Biology

Background:

  • Tumor heterogeneity and clonal evolution drive treatment resistance and progression in metastatic breast cancer (MBC).
  • The precise mechanisms of clonal evolution and their prognostic implications in MBC remain incompletely understood.

Purpose of the Study:

  • To investigate the clonal evolution patterns in MBC using circulating tumor DNA (ctDNA) analysis.
  • To develop and validate a novel indicator, the tumor clonal evolution rate (TER), for predicting treatment efficacy and patient prognosis in MBC.

Main Methods:

  • A multicenter retrospective study involving 406 MBC patients who underwent next-generation sequencing.
  • Clonal evolution was inferred using PyClone and CITUP software, analyzing ctDNA data.
  • The tumor clonal evolution rate (TER) was introduced and evaluated as a prognostic biomarker.

Main Results:

  • Branched clonal evolution was prevalent in MBC, associated with slower disease progression (HR 0.53).
  • A lower tumor clonal evolution rate (TER-low) correlated with significantly improved progression-free survival (PFS) and overall survival (OS) in both training and validation cohorts.
  • TER demonstrated prognostic value, with TER-low patients exhibiting better survival outcomes (e.g., OS HR 0.45 in training cohort).

Conclusions:

  • Branched clonal evolution in MBC is associated with superior treatment efficacy compared to linear evolution.
  • The tumor clonal evolution rate (TER) shows promise as a predictive biomarker for treatment efficacy and prognosis in metastatic breast cancer.
  • ctDNA analysis provides valuable molecular insights for predicting treatment outcomes in MBC.