How pregnancy at early age protects against breast cancer

Trends Mol Med. 2014 Mar;20(3):143-53. doi: 10.1016/j.molmed.2013.11.002. Epub 2013 Dec 16.


Pregnancy at an early age has a strong protective effect against breast cancer in humans and rodents. Postulated mechanisms underlying this phenomenon include alterations in the relative dynamics of hormone and growth factor-initiated cell fate-determining signaling pathways within the hierarchically organized mammary gland epithelium. Recent studies in epithelial cell subpopulations isolated from mouse and human mammary glands have shown that early pregnancy decreases the proportion of hormone receptor-positive cells and causes pronounced changes in gene expression as well as decreased proliferation in stem/progenitor cells. The changes include downregulation of Wnt and transforming growth factor β (TGFβ) signaling. These new findings highlight the importance of cell-cell interactions within the mammary gland epithelium in modulating cancer risk and provide potential targets for breast cancer prevention strategies.

Keywords: TGFβ signaling; Wnt signaling; breast development; hormone receptors; mammary stem/progenitor cells; pregnancy.

Publication types

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

MeSH terms

  • Age Factors*
  • Animals
  • Breast Neoplasms / prevention & control*
  • Cell Differentiation
  • Cell Proliferation
  • Epithelial Cells / metabolism
  • Female
  • Humans
  • Mammary Glands, Animal / cytology
  • Mammary Glands, Animal / metabolism
  • Mammary Glands, Human / cytology
  • Mammary Glands, Human / metabolism
  • Mice
  • Parity
  • Pregnancy*
  • Stem Cells / metabolism
  • Transforming Growth Factor beta / metabolism
  • Wnt Signaling Pathway


  • Transforming Growth Factor beta