The mammary stem cell hierarchy: a looking glass into heterogeneous breast cancer landscapes

Endocr Relat Cancer. 2015 Dec;22(6):T161-76. doi: 10.1530/ERC-15-0263. Epub 2015 Jul 23.


The mammary gland is a dynamic organ that undergoes extensive morphogenesis during the different stages of embryonic development, puberty, estrus, pregnancy, lactation and involution. Systemic and local cues underlie this constant tissue remodeling and act by eliciting an intricate pattern of responses in the mammary epithelial and stromal cells. Decades of studies utilizing methods such as transplantation and lineage-tracing have identified a complex hierarchy of mammary stem cells, progenitors and differentiated epithelial cells that fuel mammary epithelial development. Importantly, these studies have extended our understanding of the molecular crosstalk between cell types and the signaling pathways maintaining normal homeostasis that often are deregulated during tumorigenesis. While several questions remain, this research has many implications for breast cancer. Fundamental among these are the identification of the cells of origin for the multiple subtypes of breast cancer and the understanding of tumor heterogeneity. A deeper understanding of these critical questions will unveil novel breast cancer drug targets and treatment paradigms. In this review, we provide a current overview of normal mammary development and tumorigenesis from a stem cell perspective.

Keywords: breast; cancer stem cells; cell signalling; mammary gland; stem cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Breast / cytology*
  • Breast / embryology
  • Breast / growth & development
  • Breast Neoplasms / pathology*
  • Cell Differentiation
  • Cell Lineage
  • Cell Self Renewal
  • Epithelial Cells / classification
  • Epithelial Cells / cytology
  • Estrogens / physiology
  • Female
  • Heterografts
  • Humans
  • Lactation
  • Mammary Glands, Animal / cytology
  • Mammary Glands, Animal / embryology
  • Mammary Glands, Animal / growth & development
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Morphogenesis
  • Neoplasms, Hormone-Dependent / pathology
  • Neoplastic Stem Cells / cytology*
  • Organ Specificity
  • Paracrine Communication
  • Pregnancy
  • Progesterone / physiology
  • Puberty
  • Receptors, Estrogen / physiology
  • Receptors, Progesterone / physiology
  • Signal Transduction
  • Stem Cell Transplantation
  • Stem Cells / cytology*


  • Estrogens
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Progesterone