Current Standards and Future Outlooks in Metastatic Her2-Positive Breast Cancer

Approximately 20% of all breast cancer cases show overexpression or amplification of the human epidermal growth factor receptor 2 (Her2) [Cancer Epidemiol Biomarkers Prev. 2017;26(4):632-41]. With the introduction of trastuzumab, lapatinib, and pertuzumab to the realm of treatment, a new era of antibody-drug conjugates had only begun. Within the last two decades, survival for patients with this tumor subtype has fundamentally improved.

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 tyrosine kinase inhibitor in combination with capecitabine and trastuzumab, there is one efficient line of treatment available after trastuzumab deruxtecan 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.

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 [N Engl J Med. 2020;382(7):597-609]. Curing Her2-positive metastatic breast cancer, or at least living a long life with this disease, is increasingly becoming a reality.