Abstract: One third of all breast cancers are estrogen receptor alpha (ER?) negative, have a poor overall prognosis and do not respond well to currently available endocrine therapies. Use of a Wnt5-? protein or a peptide thereof, such as a recombinant Wnt-5a protein or a Wnt-5a derived hexapeptide (Foxy-5) possessing Wnt-5a signaling properties, enables restoration of ER? expression and makes it possible to treat such breast cancers with selective estrogen receptor modulators, such as tamoxifen, or aromatase inhibitors.