ESR1 and cancer: For example, ER− breast cancer patients have higher insulin like growth factor binding proteins levels than ER+ patients.[26] Elevated expression of IGF-IR or Insulin receptor substrate 1 (IRS-1) appears to increase drug- and radio-resistance of breast cancer cells and favor cancer recurrence.[25, 27] Insulin receptor substrate 1 (IRS-1) is important in transmitting IGF-IR signals to counteract ER apoptotic effect through the PI-3K/Akt survival pathways, and its stabilization improved survival of breast cancer cells in the presence of IGF-I.[28]