HER2-positive breast cancer is an aggressive subtype identified in the 1980s. The development of therapies targeting the HER2 has improved outcomes. The current standard of care, established in 2012 is dual blockade with trastuzumab + pertuzumab as first-line followed by TDM-1 as second-line. Several suboptimal choices are available in third-line or more. In 2019 the presentation of several trials evaluating new drugs and regimens in third-line has re-opened questions about sequencing, treatment of triple positive disease and treatment choice after exposure to TDM-1. These include tucatinib, neratinib and trastuzumab-deruxtecan. Other agents - including other antibody drug conjugates and bispecific antibodies as well as combinations - will lead to further changes in coming years. Additionally, should the numerous putative biomarkers thus identified ever come into use at the clinic, choice of treatment and response evaluation may be substantially changed.
Keywords: Advanced breast cancer; Anti-HER2 treatments; Biomarkers; HER2-positive disease; Sequential treatment.
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