The ovarian
hormones progesterone and
estrogen play important roles in
breast cancer etiology, proliferation, and treatment.
Androgens may also contribute to
breast cancer risk and progression. In recent years, significant advances have been made in defining the roles of these
steroid hormones in stem cell homeostasis in the breast. Stem cells are potential origins of
breast cancer and may dictate
tumor phenotype. At least a portion of breast
cancers are proposed to be driven by cancer stem cells (CSCs), cells that mimic the self-renewing and repopulating properties of normal stem cells, and can confer drug resistance.
Progesterone has been identified as the critical
hormone regulating normal murine mammary stem cell (MaSC) populations and normal human breast stem cells.
Synthetic progestins increase human
breast cancer risk; one theory speculates that this occurs through increased stem cells.
Progesterone treatment also increases breast CSCs in established
breast cancer cell lines. This is mediated in part through
progesterone regulation of
transcription factors, signal transduction pathways, and
microRNAs. There is also emerging evidence that
estrogens and
androgens can regulate breast CSC numbers. The evolving concept that a breast CSC phenotype is dynamic and can be influenced by cell signaling and external cues emphasizes that
steroid hormones could be crucial players in controlling CSC number and function. Here we review recent studies on
steroid hormone regulation of breast CSCs, and discuss mechanisms by which this occurs.