Onkologie. 2024:18(1):32-38 | DOI: 10.36290/xon.2024.007

HER-2 low breast cancer

Adam Paulík

Lékařská fakulta, Univerzita Karlova v Hradci Králové

Klinika onkologie a radioterapie, Fakultní nemocnice Hradec Králové

HER-2 low breast cancer is newly established term of completely heterogeneous subgroup of breast cancer sharing one common phenotype which is low to moderate expression of HER-2 protein and not meeting criteria for HER-2 positivity. The specific attribute of this subgroup is high responsiveness to antibody-drug conjugates (ADC´s) that can cause bystander killing effect (ADC´s of the 3^rd generation - especially T-DXd) in comparison to older ADC´s lacking this disposition (T-DM1) and to monoclonal antibodies (trastuzumab, pertuzumab, margetuximab) with almost zero efficacy due to the absence of oncogenic HER-2 signalling in HER-2 low tumours. HER-2 ultra-low subtype is defined as ≤ 10% of infiltrating cancer cells showing incomplete and faint/weak membrane staining with proven efficacy of T-DXd as well. Due to the frequent HER-2 heterogenity during the course of time the re-biopsy approach is of crucial importance to reassess the up-to-date HER-2 status enabling subsequent treatment with T-DXd.

Keywords: breast cancer subtypes, HER-2 low, ADC (antibody-drug conjugate), trastuzumab-deruxtecan (T-DXd), bystander effect, intersticial pneumonitis.

Accepted: February 22, 2024; Published: February 28, 2024  Show citation