HER2-Positive Early Breast Cancer: Time for Ultimate De-Escalation?

Simple Summary In the quest for de-escalation strategies, the complete elimination of non-targeted cytotoxic chemotherapy is often considered the ultimate goal in oncological therapy. This is particularly evident in HER2-positive breast cancer, where expanding targeted anti-HER2 therapy is a focal point of the current research due to the groundbreaking success achieved with trastuzumab. At present, several ongoing studies are examining chemotherapy-free regimens as part of initiatives to minimize the morbidity and toxic side effects of HER2-positive early breast cancer, while ensuring high oncogenic safety. Despite the promising early results achieved by these studies, the standard of care still entails combining anti-HER2 treatment with a chemotherapy backbone.Abstract De-escalation is currently taking place in both the surgical and systemic treatment of breast cancer. The introduction of trastuzumab, the first monoclonal antibody against the HER2 receptor, over 20 years ago was a milestone in the treatment of HER2-positive breast cancer and marked the beginning of a new era in targeted tumor therapy. In the sense of de-escalation, omitting non-targeted cytotoxic chemotherapy altogether is often hailed as the ultimate goal of oncological research. Especially in cases of small, node-negative, HER2-positive early breast cancer, it remains a challenge for clinicians to establish the safest and most efficient treatment plan while considering the significant potential for toxic side effects associated with chemotherapy and HER2-targeted therapy, and the generally excellent prognosis. In this context, several ongoing studies are currently assessing chemotherapy-free regimens as part of strategies aimed at de-escalating therapy in the field of HER2-positive early breast cancer. Despite the promising early results of these studies, the combination of anti-HER2 treatment with a chemotherapy backbone remains the standard of care.