The invention provides a method of screening for a compound that modulates RIZ histone methyltransferase (HMT) activity, by contacting a RIZ or RIZ fragment having HMT activity with one or more candidate compounds, and determining histone methyltransferase activity of the contacted RIZ or RIZ fragment. Also provided is a method of screening for a compound that modulates progesterone receptor (PR) activity, by providing a RIZ1 modulatory compound, and determining the ability of the RIZ1 modulatory compound to modulate PR activity. Further provided is a method of identifying an individual with an estrogen receptor positive (ER+) tumor having a reduced likelihood of responding to endocrine therapy. The method involves determining the RIZ1 status of the tumor, wherein an abnormal RIZ1 status identifies the individual as an individual with a reduced likelihood of responding to endocrine therapy.