Molecular mechanisms of metastasis in breast cancer--clinical applications

Nat Rev Clin Oncol. 2010 Dec;7(12):693-701. doi: 10.1038/nrclinonc.2010.171. Epub 2010 Oct 19.


The metastatic cascade is a series of biological processes that enable the movement of tumor cells from the primary site to a distant location and the establishment of a new cancer growth. Circulating tumor cells (CTCs) have a crucial role in tumor dissemination. The role of CTCs in treatment failure and disease progression can be explained by their relation to biological processes, including the epithelial-to-mesenchymal transition and 'self seeding', defined as reinfiltration of the primary tumor or established metastasis by more aggressive CTCs. CTCs are a unique and heterogeneous cell population with established prognostic and predictive value in certain clinical situations. The possibility of collecting sequential blood samples for real-time monitoring of systemic-therapy efficacy presents new possibilities to evaluate targeted therapies based on the genomic profiling of CTCs and to improve the clinical management of patients by personalized therapy. Interruption of the metastatic cascade via the targeting of CTCs might be a promising therapeutic strategy.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers, Tumor
  • Breast Neoplasms / blood
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / therapy
  • Cell Movement
  • Disease Progression
  • Epithelial-Mesenchymal Transition
  • Female
  • Humans
  • Mammary Neoplasms, Experimental / pathology
  • Matrix Metalloproteinases / physiology
  • Molecular Targeted Therapy
  • Neoplasm Invasiveness
  • Neoplasm Metastasis / physiopathology*
  • Neoplasm Proteins / blood
  • Neoplasm Proteins / physiology
  • Neoplastic Cells, Circulating / chemistry
  • Neoplastic Cells, Circulating / pathology*
  • Precision Medicine
  • Prognosis
  • Receptors, Chemokine / physiology
  • Receptors, Urokinase Plasminogen Activator / physiology
  • Stromal Cells / physiology
  • Treatment Failure


  • Biomarkers, Tumor
  • Neoplasm Proteins
  • Receptors, Chemokine
  • Receptors, Urokinase Plasminogen Activator
  • Matrix Metalloproteinases