LABORATORY RESEARCH MicroRNA-Antagonism Regulates Breast Cancer Stemness and Metastasis via TET-Family-Dependent Chromatin Remodeling The authors found microRNA (miR)-22 triggers epithelial-mesenchymal transition, enhances invasiveness and promotes metastasis in mouse xenografts. In a conditional mammary gland-specific transgenic mouse model, we show that miR-22 enhances mammary gland side-branching, expands the stem cell compartment, and promotes tumor development. [Cell] Abstract | Graphical Abstract | Press Release Estrogen Alters the Splicing of Type 1 Corticotropin-Releasing Hormone Receptor in Breast Cancer Cells The role of the stress hormone corticotropin-releasing hormone (CHR) in breast cancer is complex, and its abundance and biological activity may be modulated by estrogen. In the estrogen receptor-positive malignant mammary epithelial cell line MCF7, CRH activated numerous kinases and downstream effectors, at least some of which were mediated by the CRH receptor type 1. [Sci Signal] Abstract Breast Cancer Normalization Induced by Embryonic Mesenchyme Is Mediated by Extracellular Matrix Biglycan Using a synthetic reconstitution system, scientists showed that co-culture of breast cancer cells with embryonic mesenchyme from early stage mammary glands decreases tumor cell proliferation while stimulating acinus differentiation, whereas cancer-associated fibroblasts fail to produce these normalizing effects. [Integr Biol] Abstract Sox2 Suppresses the Invasiveness of Breast Cancer Cells via a Mechanism that is Dependent on Twist1 and the Status of Sox2 Transcription Activity While the aberrant expression of Sox2 has been shown to significantly correlate with a number of clinicopathologic parameters in breast cancer (BC), its biological significance in BC is incompletely understood. In-vitro invasion assay was used to evaluate whether the expression of Sox2 is linked to the invasiveness of MCF7 and ZR751 cells. [BMC Cancer] Abstract | Full Article Histone Deacetylase 4 Mediates SMAD Family Member 4 Deacetylation and Induces 5-Fluorouracil Resistance in Breast Cancer Cells The authors investigated the interaction between HDAC4 expression and chemoresistance in breast cancer cells. They found that increased histone deacetylase 4 expression in MDA-MB-231 cells was associated with resistance to the anticancer drug 5-fluorouracil. [Oncol Rep] Abstract Aurora A Kinase Regulates Mammary Epithelial Cell Fate by Determining Mitotic Spindle Orientation in a Notch-Dependent Manner Scientists examined the role of the mitotic kinase Aurora A (AURKA) in regulating the balance between basal and luminal mammary lineages. They found that AURKA is highly expressed in basal stem cells and, to a lesser extent, in luminal progenitors. Wild-type AURKA expression promoted luminal cell fate, but expression of an S155R mutant reduced proliferation, promoted basal fate, and inhibited serial transplantation. [Cell Rep] Abstract | Graphical Abstract | Full Article CLINICAL RESEARCH N0539 Phase II Trial of Fulvestrant and Bevacizumab in Patients with Metastatic Breast Cancer Previously Treated with an Aromatase Inhibitor: A North Central Cancer Treatment Group Trial Based on preclinical studies, the vascular endothelial pathway is an important mechanism for estrogen receptor resistance. Researchers conducted a phase II study of fulvestrant and bevacizumab in patients with aromatase inhibitor pretreated metastatic breast cancer. A single-stage phase II study was conducted with these objectives: six-month progression-free survival, tumor response, toxic effect, and overall survival. [Ann Oncol] Abstract A Randomized Phase II Pre-Surgical Trial of Weekly Low-Dose Tamoxifen versus Raloxifene versus Placebo in Premenopausal Women with Estrogen Receptor Positive Breast Cancer The authors conducted a randomized trial testing tamoxifen (T) 10mg per week (w), vs raloxifene (R) 60 mg/d vs placebo in a pre-surgical model. The participants were all premenopausal women with estrogen receptor-positive breast cancer. They were randomly assigned to either T 10mg/w or R 60 mg/d or placebo for six weeks before surgery. The primary endpoint was tissue change of Ki67. [Breast Cancer Res] Abstract | Full Article |