ESR1 and breast cancer: Besides adjuvant ET, numerous questions arise concerning the following: (a) when should NAC therapy be proposed for patients with ER-low BC and which is the optimal regimen; (b) should the majority of the patients with ER-low BC receive adjuvant chemotherapy; and (c) what is the role of adjuvant cyclin-dependent kinase (CDK)4/6 inhibitor therapy, which has been recently introduced in high-risk patients with ER-positive BC [44].