The breast tumor microenvironment: role in cancer development, progression and response to therapy

Abstract

Numerous clinical and pre-clinical studies have provided ample evidence supporting that the tumor microenvironment plays a significant role during breast cancer development, progression and in determining the therapeutic response. Areas covered: This review focuses on the evolving concept of the microenvironment as the critical participant in each step of the multi-stage process of malignant progression. Currently, only a small number of molecules form part of routine molecular diagnostics in breast caner, but microenvironment-derived biomarkers are potential additions to existing predictive and prognostic marker panels. The authors discuss the dependency of the breast tumor cells on different components of the microenvironment for their survival, dissemination, dormancy and establishment in secondary sites to form overt metastasis, as well as the potential as a therapeutic target to improve breast cancer outcome. Expert commentary: Despite the importance in the development of breast cancer, the contribution of the microenvironment is not considered in routine diagnostic testing or informing therapeutic decisions. However, introduction of immunotherapy will increasingly require patient selection based on the stromal composition of the primary breast tumor. Better understanding of the role of specific microenvironment-derived molecules is likely to inform personalized therapy, leading to improved patient outcome.

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

“…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 ]. On the other hand, released factors from cancer-associated fibroblasts (CAF) and adipocytes (CAA) contribute to the tumorigenic phenotype of pre-malignant and malignant epithelial cells [ 4 ] promoting tumor cell proliferation, invasiveness, and growth. 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 ].…”

Identification of genes with therapeutic and prognostic values in lung adenocarcinoma microenvironment

“…In pancreatic tumor tissues, the higher proportions of CD4 + and CD8 + T cells, the better long-term prognosis for patients [40]. In breast carcinoma, annexin1 promoted polarization of M1 macrophages and induced pro-inflammatory genes [41]. Nevertheless, it was reported that the higher numbers of T or B cells, the worse capsular and perineural invasion in prostate cancer [42].…”

The role of exosomal long non-coding RNAs in cancer drug resistance

“…These sites are known as pre-metastatic niches (PMNs). One of the main factors regarding metastasis is the generation of these preordained areas which enable the cells to succeed in their migration [8,9,15,16] . In addition, drugresistant clones in the primary tumor are more competent to undergo epithelial-mesenchymal transition (EMT) and present higher probabilities to reach a favorable PMN [5] .…”