Approximately 15-20% of breast
cancers (BC) demonstrate HER2 overexpression/gene amplification. Historically, before the era of HER2-directed
therapies, this subtype was associated with poor prognosis. Anti-HER2 agents dramatically changed the natural course of disease and significantly prolonged patients' survival. In recent years, a number of new anti-HER2
therapies have been developed, and their approvals offer new therapeutic options for patients with advanced HER2-positive
breast cancer. At present, HER2 pathway blocking drugs used in the treatment of metastatic
breast cancer worldwide include
trastuzumab and
pertuzumab in the first-line treatment;
trastuzumab deruxtecan and
trastuzumab emtansine in the second line; and
tucatinib,
neratinib,
lapatinib, and
margetuximab in further lines of treatment of advanced HER2 positive
breast cancer. Additionally, there are many clinical trials underway evaluating drugs blocking the HER2 pathway in advanced disease setting. This article presents new treatment options, discussing the most important findings from clinical trials and real-world reports, clinical benefits and risks of treatment, as well as efficacy of re-treatment with
trastuzumab in metastatic
breast cancer. New data challenge the current standards, and a number of questions arise regarding the optimal sequence of anti-HER2 targeted
therapies, the optimal combination, including endocrine agents in
luminal HER2 positive
tumors and treatment of special patient population such as patients with
brain metastases (BM).