How pregnancy at early age protects against breast cancer

• Early pregnancy protects against breast cancer in humans and rodents.
• Parity reduces protumorigenic Wnt signaling in stem/progenitor cells.
• Early pregnancy alters quiescent state-inducing TGFβ signaling.
• Parity decreases the proliferation of stem/progenitor cells.

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.