ABSTRACT
Although many advances have been made in the treatment of breast cancer, for the triple negative breast cancer (TNBC) these therapies have not significantly increased overall survival. Tumor microenvironment (TME) plays an essential role to develop and control TNBC progression. Many preclinical and clinical studies are ongoing to treat patients with TNBC disease, but the effective therapies are currently not available. Here, we have reviewed recent progress in understanding of TNBC and advance in defining mechanisms of TNBC therapies and potential therapeutic strategies to overcome TNBC.
Subject(s)
Triple Negative Breast Neoplasms , Humans , Triple Negative Breast Neoplasms/pathology , Signal Transduction , Tumor MicroenvironmentABSTRACT
Combined oral contraceptives (COCs) are commonly used by individuals for contraceptive and noncontraceptive purposes, such as the management of dysmenorrhea or to reduce risk for ovarian and endometrial cancer. However, a common consideration that continues to arise is whether COC use increases breast cancer risk. Many researchers have investigated this, but study results are varied and may be affected by variables such as hormone type, an individual's age, and the duration of COC use. In this article, we summarize select breast cancer risk considerations regarding COC use to assist clinicians when counseling individuals considering using oral contraceptives.
Subject(s)
Breast Neoplasms , Contraceptives, Oral, Combined , Breast Neoplasms/chemically induced , Contraceptives, Oral, Combined/adverse effects , Dysmenorrhea , Female , Humans , RiskABSTRACT
In triple-negative breast cancer (TNBC), the lack of therapeutic markers and effective targeted therapies result in an incurable metastatic disease associated with a poor prognosis. Crosstalks within the tumor microenvironment (TME), including those between cancer and stromal cells, affect the tumor heterogeneity, growth, and metastasis. Previously, we have demonstrated that IL-6, IL-8, and CCL5 play a significant role in TNBC growth and metastasis. In this study, we performed a systematic analysis of cytokine factors secreted from four stromal components (fibroblasts, macrophages, lymphatic endothelial cells, and blood microvascular endothelial cells) induced by four TNBC cell types. Through bioinformatic analysis, we selected putative candidates of secreted factors from stromal cells, which are involved in EMT activity, cell proliferation, metabolism, and matrisome pathways. Among the candidates, LCN2, GM-CSF, CST3, IL-6, IL-8, and CHI3L1 are ranked highly. Significantly, Lipocalin-2 (LCN2) is upregulated in the crosstalk of stromal cells and four different TNBC cells. We validated the increase of LCN2 secreted from four stromal cells induced by TNBC cells. Using a specific LCN2 antibody, we observed the inhibition of TNBC cell growth and migration. Taken together, these results propose secreted factors as molecular targets to treat TNBC progression via crosstalk with stromal components.
