Although these therapeutics are yet to be evaluated in human breast cancer trials, data obtained from cell culture and mouse models suggests ER+ breast cancers with PIK3CA-mutations and/or increased INPP4B expression may benefit from Wnt therapies in combination with current standard-of-care treatments, whereas ER− breast cancers may respond to combination therapy of Wnt and PI3K/mTOR inhibition to prevent Wnt reactivation. The gene discussed is ESR1; the disease is breast carcinoma.