The Tumor Microenvironment as a Regulator of Endocrine Resistance in Breast Cancer

Abstract

Estrogen receptor positive breast neoplasias represent over 70% of diagnosed breast cancers. Depending on the stage at which the tumor is detected, HER2 status and genomic risk, endocrine therapy is combined with either radio, chemo and/or targeted therapy. A growing amount of evidence supports the notion that components of the tumor microenvironment play specific roles in response to treatment and that strategies targeting these key interactions with tumor cells could pave the way to a new generation of therapies. In this review, we analyze the evidence suggesting different components of the tumor microenvironment play a role in hormone receptor positive breast cancer progression. In particular we focus on the immune system, carcinoma associated fibroblasts and the extracellular matrix. Further insight into the cross talk between these constituents of the microenvironment and the tumor cells may lead to therapies that eliminate disseminated metastatic cells early on, and thus reduce distant disease relapse which is the leading cause of death for patients who are diagnosed with this illness.

Extracellular Neuroglobin as a Stress-Induced Factor Activating Pre-Adaptation Mechanisms against Oxidative Stress and Chemotherapy-Induced Cell Death in Breast Cancer

“…Tumor microenvironment encompasses a complex mixture of cancer and non-cancerous cells (i.e., immune and endothelial cells, fibroblasts, adipocytes) and the extracellular matrix (ECM) [ 1 , 2 , 3 ]. A binary intertwined connection exists between all the components of tumor microenvironment as demonstrated in breast cancer (BC) [ 2 , 3 ].…”

“…Tumor microenvironment encompasses a complex mixture of cancer and non-cancerous cells (i.e., immune and endothelial cells, fibroblasts, adipocytes) and the extracellular matrix (ECM) [ 1 , 2 , 3 ]. A binary intertwined connection exists between all the components of tumor microenvironment as demonstrated in breast cancer (BC) [ 2 , 3 ]. On one side, tumor cells directly interact each other and sculpt the ECM by releasing a variety of proteins that act as autocrine or paracrine factors influencing cancer and non-cancer cell proliferation, differentiation, and survival [ 1 ].…”

“…In addition, CAF-released factors influence the development of therapy resistance by inducing anti-apoptotic mechanisms in both estrogen receptor α positive (ERα+) and negative (ERα−) breast cancer cells exposed to anti-cancer drugs [ 5 , 6 ]. Moreover, the direct role of BC-associated fibroblasts in reducing hormone sensitivity and increasing resistance to endocrine therapy (i.e., Tamoxifen) has been demonstrated in ERα+ breast cancer cells [ 2 , 6 ]. The effect of heterotypic interaction between epithelial breast cancer cells and non-cancerous stromal cells have attracted major research interests focused in the discovery of new druggable pathways involved in cancer cell adaptation/resistance to stressful conditions and therapeutic strategies [ 1 , 2 , 4 ].…”

“…Moreover, the direct role of BC-associated fibroblasts in reducing hormone sensitivity and increasing resistance to endocrine therapy (i.e., Tamoxifen) has been demonstrated in ERα+ breast cancer cells [ 2 , 6 ]. The effect of heterotypic interaction between epithelial breast cancer cells and non-cancerous stromal cells have attracted major research interests focused in the discovery of new druggable pathways involved in cancer cell adaptation/resistance to stressful conditions and therapeutic strategies [ 1 , 2 , 4 ]. However, the identification of molecular factors and mechanisms by which cancer cells may affect the extracellular milieu and, in turn, neighbor normal and/or cancer epithelial cells in homotypic way is still in its infancy.…”

A novel culture method that sustains ERα signaling in human breast cancer tissue microstructures

“…It is a heterogeneous disease with distinct biological features and clinical outcomes. Almost 75% of diagnosed BC express estrogen receptor-alpha (ERα), being classified as ERα-positive (ER+) BC (2).…”