Propensity for Early Metastatic Spread in Breast Cancer: Role of Tumor Vascularization Features and Tumor Immune Infiltrate

Simple Summary Neoangiogenesis and different components of tumor microenvironment exert crucial roles in early metastatic spreading of breast cancer. Due to the paucity of available factors for breast cancer that can estimate the risk of metastasis or response to a given treatment, there is an important need for new, additional biomarkers of the tumor stroma that can be prognostic and predictive at the early stages of the disease. This review is focused on the current understanding of breast tumor environment characteristics (tumor vasculature and immune infiltrate) in order to incorporate them in diagnostic algorithms together with the assessment of hormone receptors (ER and PR) and of HER2 status. Breast cancer is a complex and highly heterogeneous disease consisting of various subtypes. It is classified into human epidermal growth receptor 2 (HER-2)-enriched, luminal A, luminal B and basal-like/triple negative (TNBC) breast cancer, based on histological and molecular features. At present, clinical decision-making in breast cancer is focused only on the assessment of tumor cells; nevertheless, it has been recognized that the tumor microenvironment (TME) plays a critical biologic role in breast cancer. This is constituted by a large group of immune and non-immune cells, but also by non-cellular components, such as several cytokines. TME is deeply involved in angiogenesis, immune-evasion strategies, and propensity for early metastatic spread, impacting on prognosis and prediction of response to specific treatments. In this review, we focused our attention on the early morphological changes of tumor microenvironment (tumor vasculature features, presence of immune and non-immune cells infiltrating the stroma, levels of cytokines) during breast cancer development. At the same time, we correlate these characteristics with early metastatic propensity (defined as synchronous metastasis or early recurrence) with particular attention to breast cancer subtypes.