Here, we report the results of the “Advanced Breast Cancer Estetrol” (ABCE4) study, a phase IB/IIA, dose-escalation study with E4 in postmenopausal women with progressive ER+/HER2− end-stage breast cancer with resistance or intolerance to tamoxifen or AIs without established therapeutic alternatives, including chemotherapy. Here, ERBB2 is linked to breast carcinoma.