HER2-positive breast cancer (BC), defined by HER2 gene amplification and/or overexpression at the protein level, accounts for approximately 20% of all BC cases. The use of the anti-HER2 drug trastuzumab, developed 20 years ago, changed the natural course of the disease and improved the clinical outcome. Subsequent use of “dual blockade” (trastuzumab-pertuzumab; trastuzumab-lapatinib), as well as an antibody-drug conjugate (T-DM1), improved relapse-free and overall survival of patients with HER2-positive BC. Further progress in anti-HER2 targeted therapy is associated with the use of a new generation of conjugates – trastuzumab-deruxtecan (T-Dxd). In addition, a number of clinical trials on the successful use of T-Dxd in patients with lower HER2 protein expression (HER2 1+ or 2+ with negative in situ hybridization (ISH-) levels, detected in half of BC patients have been performed.

Keywords: trastuzumab-deruxtecan, low HER2 (HER2 1+ or 2+ (ISH-) expression, breast cancer