Adjuvant Palbociclib in Elderly Patients With Breast Cancer (Appalaches) is a phase-II study to determine the efficacy of the combination of at least 5 years of endocrine therapy and 2 years of palbociclib as adjuvant treatment in place of adjuvant chemotherapy followed by endocrine therapy in older (≥70 years) patients with ER-positive, HER2-negative early breast cancer stages II-III [34]. Here, ESR1 is linked to breast cancer.