The role of intratumoral and systemic IL-6 in breast cancer

Breast Cancer Res Treat. 2013 Apr;138(3):657-64. doi: 10.1007/s10549-013-2488-z. Epub 2013 Mar 27.


Chronic low-grade inflammation plays an important role in the pathogenesis of several cancer forms including breast cancer. The pleiotropic cytokine IL-6 is a key player in systemic inflammation, regulating both the inflammatory response and tissue metabolism during acute stimulations. Here, we review the associations between IL-6 and breast cancer ranging from in vitro cell culture studies to clinical studies, covering the role of IL-6 in controlling breast cancer cell growth, regulation of cancer stem cell renewal, as well as breast cancer cell migration. Moreover, associations between circulating IL-6 and risk of breast cancer, prognosis for patients with prevalent disease, adverse effects and interventions to control systemic IL-6 levels in patients are discussed. In summary, direct application of IL-6 on breast cancer cells inhibits proliferation in estrogen receptor positive cells, while high circulating IL-6 levels are correlated with a poor prognosis in breast cancer patients. This discrepancy reflects distinct roles of IL-6, with elevated systemic levels being a biomarker for tumor burden, physical inactivity, and impaired metabolism, while local intratumoral IL-6 signaling is important for controlling breast cancer cell growth, metastasis, and self renewal of cancer stem cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Female
  • Humans
  • Interleukin-6 / pharmacology
  • Interleukin-6 / physiology*
  • Receptors, Estrogen / metabolism
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction


  • IL6 protein, human
  • Interleukin-6
  • Receptors, Estrogen
  • STAT3 Transcription Factor
  • STAT3 protein, human