Tumor microenvironment is a key driver for drug delivery and efficacy in HER2+ breast cancer

Introduction: Tumor-targeted therapies are typically given to cancer patients whose tumors overexpress markers that can be targeted to selectively destroy cancer cells. Human epidermal growth factor receptor 2 (HER2) overexpression in breast cancer, treatable with monoclonal antibodies like trastuzumab, is a key example. However, ~40% of patients with HER2 overexpression fail to achieve complete tumor regression (Fig.1A) (1). We investigated whether tumor microenvironment (TME) features, such as vascularization and immune cell infiltration (2,3), influence treatment efficacy beyond HER2 expression (Fig.1B).