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  3. Evolutionary History Of Metastatic Breast Cancer Reveals Minimal Seeding From Axillary Lymph Nodes.
  1. Home
  3. Evolutionary History Of Metastatic Breast Cancer Reveals Minimal Seeding From Axillary Lymph Nodes.

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Evolutionary history of metastatic breast cancer reveals minimal seeding from axillary lymph nodes.

Ikram Ullah1, Govindasamy-Muralidharan Karthik1, Amjad Alkodsi2

  • 1Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden.

The Journal of Clinical Investigation
|February 27, 2018

View abstract on PubMed

Summary
This summary is machine-generated.

Genomic analysis of metastatic breast cancer reveals diverse tumor evolution and seeding patterns. Axillary lymph node metastasis does not seed distant sites, suggesting hematogenous spread and highlighting evolving APOBEC-associated mutagenesis.

Keywords:
Breast cancerGeneticsLymphMolecular geneticsOncology

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Area of Science:

  • Oncology
  • Genomics
  • Cancer Evolution

Background:

  • Metastatic breast cancer remains incurable, necessitating a deeper understanding of tumor progression.
  • Characterizing the evolutionary dynamics of metastasis is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the genomic evolutionary landscape of metastatic breast cancer.
  • To determine the role of axillary lymph nodes (ALNs) in seeding distant organ metastasis.
  • To elucidate evolving mutational processes during cancer progression.

Main Methods:

  • Comprehensive genomic analysis of primary tumors and metastatic lesions from 20 breast cancer patients (99 samples).
  • Evolutionary modeling to infer tumor spreading and seeding patterns.
  • Analysis of mutational processes, including APOBEC-associated mutagenesis.

Main Results:

  • Identified diverse evolutionary patterns, including linear and parallel evolution to distant metastatic sites.
  • Demonstrated polyclonal seeding, with multiple subclones originating from primary tumors and/or metastases.
  • Found that synchronous ALN metastasis does not contribute to distant seeding, suggesting hematogenous dissemination.
  • Observed co-occurrence of clonal evolution with new driver alterations and increased APOBEC-associated mutagenesis.

Conclusions:

  • Axillary lymph node metastasis is not a significant route for seeding distant organ metastasis in breast cancer.
  • Hematogenous spread is a primary mechanism for distant cancer dissemination.
  • Genomic evolution during metastasis involves changing mutational landscapes and driver alterations.