ESR2 and breast cancer: Previous studies have shown that PHB is mainly localized and functions within the mitochondria,17 and we found that mitochondrial PHB translocates to the nucleus in the presence of ERα in androgen-independent prostate cancer PC3 cells.19 In BC cells, it was reported that ERα suppresses BC initiation and invasion, whereas ERβ promotes BC initiation and progression.40 Mechanistic studies suggest that ERα and ERβ exert these effects via modulation of the Akt pathway and DNA replication complex.41, 42 Yet, it remains unclear how PHB is delivered to the mitochondria in BC cells.