ER-α has a well-established role in supporting estrogendependent breast tumor growth through its association with aberrant proliferation (up-regulating Ki-67), which can result in the accumulation of random DNA mutations (marked by γH2AX), and when highly expressed it is associated with poor prognosis in breast cancer (25, 26), which can explain the aggressive breast cancer subtype observed when EYA4 is over-expressed. The gene discussed is ESR1; the disease is breast cancer.