HER2-targeted agents are the central component of HER2-positive metastatic breast cancer (MBC) treatment. The combination of trastuzumab, pertuzumab and a taxane is the preferred first-line regimen in most settings. For patients with disease relapse after adjuvant therapy, treatment decisions in the first-line are influenced by the treatment-free interval and the regimens used in the (neo)adjuvant setting. T-DXd has been recently established as the preferred second-line therapy. T-DM1, or the combination of tucatinib, trastuzumab and capecitabine, are reasonable third-line options, although efficacy and safety data of these regimens after prior exposure to T-DXd are lacking. In fourth and later lines, trastuzumab duocarmazine, neratinib plus capecitabine, margetuximab plus chemotherapy, lapatinibbased combinations or the continuation of trastuzumab with different chemotherapy partners are valid alternatives.

(BELG J MED ONCOL 2022;16(6): PUBLICATION AHEAD OF PRINT)