ESR1 and breast cancer: For many years, tamoxifen was the mainstayof endocrine treatment for ER+ breast cancer(47), but recently the third-generation aromataseinhibitors (AIs) called estrogen receptordown- regulators (ERDs) such as fulvestrant(Faslodex) have started to be used ahead of tamoxifenin the first-line advanced (48) and adjuvant(49) settings because of their superior efficacyand tolerability profiles.