Ethinyl estradiol(EE2)therapy has been reported to be an effective endocrine therapy for postmenopausal hormone receptor-positive advanced breast cancer, especially in the supposed acquired resistance state. The current study retrospectively investigated the efficacy and safety of EE2 therapy in postmenopausal women with hormone receptor-positive advanced breast cancer who had previously undergone multiple endocrine therapies. Twelve patients were enrolled; median lines of endocrine therapies were seven before EE2. Median PFS was 4.8 months and median overall survival was 10.0 months. Grade 3 adverse event comprised of anorexia in only one patient. EE2 therapy may be considered effective and safe in hormone receptor-positive advanced breast cancer even in late-stage endocrine therapy.