However, NRG2 median expression is increased up to three-fold in estrogen receptor (ER) and progesterone receptor (PR) negative tumors compared to ER- and PR-positive samples.[84] A different study found expression of HER3 ligands (NRG1 and NRG2) in 39.3% of samples and HER4 ligands (NRG1-4, EREG, BTC, HB-EGF) in 74.1% of samples.[84] Rearrangements in the NRG1 gene were found in 17 of 382 of breast cancer cases, and an amplicon centromeric to NRG1 was found in 63 of 262 cases and correlated with poor prognosis.[85] NRG expression has been associated with both better and worse prognosis. Here, ESR1 is linked to breast cancer.