Current standards and future outlooks in metastatic Her2-positive breast cancer

Background: Approximately 20% of all breast cancer cases show overexpression or amplification of the human epidermal growth factor receptor 2 (Her2) (1). With the introduction of trastuzumab, lapatinib and pertuzumab to the realm of treatment, a new era of antibody-drug conjugates (ADCs) had only begun. 
Summary: Within the last two decades, survival for patients with this tumor subtype has fundamentally improved. With the HER2CLIMB trial, patients with brain metastasis were no longer excluded from bigger trials, and international guidelines implemented its presence or absence in their decision trees (2). Curing Her2 positive metastatic breast cancer, or at least living a long life with this disease, is increasingly becoming a reality. 
Beginning with a taxane plus trastuzumab/pertuzumab followed by trastuzumab deruxtecan, the first- and second-line treatments are set in stone. With the introduction of tucatinib as a newer TKI in combination with capecitabine and trastuzumab, there is one efficient line of treatment available after trastuzumab deruxtacan or even earlier in selected cases with active brain metastasis. 
Especially for later stages of disease, several combination strategies are under investigation. There is still a lack of positive results on immune checkpoint inhibition combined with Her2-targeted therapy, but hopefully an extension to the treatment algorithm will be on its way soon. 
Key messages: First three lines of treatment of Her2+ metastatic disease are well defined, with the sequence in second line dependent on the clinical presentation. Beyond that there is a need for better definition of treatment and clinical trials. 
