For patients with early-stage Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer (BC), the most important data presented at SABCS 2022 consisted of the final results of the phase III PEONY study. Results of this trial add to the existing body of evidence demonstrating the benefit of the pertuzumabtrastuzumab-docetaxel regimen in patients with HER2-positive early breast cancer (EBC). In the metastatic setting, trastuzumab deruxtecan (T-DXd) was once again the center of the attention with the presentation of data from the DESTINY-Breast02, DESTINY-Breast03 and ROSET-BM trials. Finally, several studies assessed the possibility of chemotherapy-free regimens for the treatment of HER2-positive, hormone receptor (HR)- positive metastatic BC.