Elf5 is an epithelial-specific ETS transcription factor essential for mammary alveolar development during pregnancy ^{1  2}  because it directs cell-fate decisions made by progenitor cells³. Recently we found that RankL, a paracrine mediator of stem cell activity controlled by progesterone, induced Elf5 expression in progenitor cells, directing the progesterone-generated stem cell flux toward alveolargenesis ^{4  5} . Elf5 specifies breast cancer subtype by suppressing estrogen action and inducing the expression of genes that define the basal phenotype⁶. When we clustered breast cancers using Elf5 ChIP targets we reproduced the subtypes seen using the Perou intrinsic classifier and separated ER+ and ER- tumours with near 100% accuracy⁶. Discovery of the direct transcriptional targets of Elf5 using ChIP-Seq revealed numerous Elf5 targets with demonstrated roles in antiestrogen resistance, such as FoxA1 (ER pioneer factor), Myc (promotes intrinsic resistance), and EGFR and IGFR1. Elf5 levels increased greatly in MCF7 cells made resistant to antiestrogens and knock down of Elf5 in antiestrogen resistant cell lines stopped their proliferation. Elf5 binds to the breast cancer genome at ETS sites (TTCC motif) coincident with FoxA1, Stat1/3 and NKX3-2 sites. This presentation will also highlight unpublished work regarding the effect of Elf5 on mammary metastasis to lung, which distinguishes cell autonomous and cell extrinsic effects of Elf5 expression by metastasizing cancer cells.