In the field of Human Epidermal Growth Factor Receptor 2 (HER2) positive early breast cancer, an interesting Subpopulation Treatment Effect Pattern Plot (STEPP) analysis of the APHINITY trial was presented at SABCS 2020. In addition, BluePrint RNA sequencing was used in an attempt to predict the benefit of adjuvant pertuzumab in this trial. Other interesting data in early HER2-positive breast cancer came from the use of neratinib as extended adjuvant therapy. In the metastatic setting, results of the PERTAIN study, the first randomised phase II trial to assess the addition of pertuzumab to trastuzumab and an aromatase inhibitor in the presence or absence of induction chemotherapy, were presented. Finally, a long list of abstracts featured results with novel HER2-directed therapies, including the antibody-drug conjugate trastuzumab deruxtecan, the tyrosine kinase inhibitor tucatinib and the investigational monoclonal antibody margetuximab.