ER-α has a well-established role in supporting estrogen-dependent 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 [30, 31], which can explain the aggressive breast cancer subtype observed when EYA4 is over-expressed. This evidence concerns the gene ESR1 and breast carcinoma.