Figure 2.

The interaction between tumor microenvironment components, including stromal cells, and tumor cells leads to enhanced cell growth, proliferation, angiogenesis and invasion. Breast cancer epithelial cells increase tumor cell proliferation and invasion while inhibiting apoptosis through either of these following pathways: (1) classical pathway in which estrogen binds to its receptor, ER, or (2) non-classical pathway that involves post-translational modifications of ER by activation kinases, and transcription factors. Anti-cancer agents including tamoxifen (TAM), whose metabolites, 4-OH TAM and endoxifen, have higher affinity for ER when compared with TAM, exert their effects by modulating signaling pathways that regulate tumor cells.Note: Data adapted from Russell³⁹ and Barone et al.⁴⁰