Long road towards effective HER3 targeting in breast cancer

Breast cancer is a heterogeneous disease, encompassing multiple different subtypes. Thanks to the increasing knowledge of the diverse biological features of each subtype, most patients receive personalized treatment based on known biomarkers. However, the role of some biomarkers in breast cancer evolution is still unknown, and their potential use as a therapeutic target is still underexplored. HER3 is a member of the human epidermal growth factors receptor family, overexpressed in 50%-70% of breast cancers. HER3 plays a key role in cancer progression, metastasis development, and drug resistance across all the breast cancer subtypes. Owing to its critical role in cancer progression, many HER3-targeting therapies have been developed over the past decade with conflicting findings. Next-generation antibody-drug conjugates have recently shown promising results in solid tumors expressing HER3, including breast cancer. In this review, we discuss the HER3 role in the pathogenesis of breast cancer and its relevance across all subtypes. We also explore the new anti-HER3 treatment strategies, calling into question the significance of HER3 detection as crucial information in breast cancer treatment.