ESR1 and breast cancer: Recently, we reported that ER− breast cancer cells expressing endogenous ER-α36 and ER+ breast cancer cells and ER− HEK293 cells expressing high levels of recombinant ER-α36 responded to a very low concentration of E2 : activation of the MAPK/ERK signaling pathway at the picomolar range, suggesting that cells expressing high levels of ER-α36 are hypersensitive to E2 .(18) Based on these results, we suggest that ER-α36 probably plays an important role in regulating bone metabolism at the low E2 levels of the postmenopausal women.