Abstract
HER2 positivity is predictive of the response to anti-HER2 therapies. The treatment
of HER2-positive tumors is continuously improving through the development of new anti-HER2-directed
agents. Many different anti-HER2 therapies are now available which belong to the classes
of anti-HER2 antibodies, tyrosine kinase inhibitors (TKI) and antibody-drug conjugates
(ADC). A combination of trastuzumab, pertuzumab and a taxane (THP) remains the preferred
first-line (1L) therapy, whereas T‑DXd is the new standard for 2L metastatic breast
cancer based on a highly significant improvement in progression-free survival compared
to T-DM1 as shown in the DESTINY-Breast03 study. A tucatinib-based regimen (dual anti-HER2
therapy with trastuzumab and tucatinib plus capecitabine) is the preferred 3L option,
which may already be used for 2L treatment in patients with active brain metastases.
Different anti-HER2 therapies are available in the 3L setting and beyond. Molecular
biomarkers in addition to the quantification of HER2 expression, such as the PD‑L1
status and PIK3CA mutations, can further guide the decision-making process in the
future.
Keywords
HER2-positive breast cancer
