INTRODUCTION: Chemotherapy combined with anti-human epidermal growth factor receptor 2 (HER2)-targeted therapy is currently a standard treatment for advanced HER2/HR-positive breast cancer (BC), although evidences showed that HR expression compromised effectiveness of the treatment. While cyclin-dependent kinase (CDK) 4/6 inhibitors combined with endocrine therapy is a key therapy for the BC with HR expression, data on the effectiveness and safety of CDK 4/6 inhibitors combined with trastuzumab and endocrine therapy as a first-line treatment for HER2-positive and HR-positive metastatic BC are limited. CASE PRESENTATION: Here, we report a case of a 46-year-old premenopausal woman diagnosed with stage 4 HER2/HR-positive invasive ductal carcinoma from both right and left breast with hypermetabolic activities in multiple lymph nodes, adrenal, bone, and skin. INTERVENTIONS: Due to the patient's refusal to use chemotherapy, she was started on goserelin, abemaciclib, letrozole, and trastuzumab. OUTCOMES: The patient's symptoms were relieved with near resolution of the primary breast mass and nearly all of the metastatic sites. Metabolic resolution was observed in bone lesions. The disease was under control for 57 weeks. During the treatment, neutropenia (grade 1-2) and anemia (grade 1) occurred, which spontaneously recovered. Additionally, diarrhea improved after symptomatic treatment. CONCLUSION: We believe that the combination of trastuzumab, hormone suppression, and abemaciclib is a practicable and effective treatment for HER2-positive and HR-positive metastatic BC in premenopausal patients who cannot tolerate the first-line chemotherapy.