LABORATORY RESEARCH Tumor Microenvironment-Based Feed-Forward Regulation of NOS2 in Breast Cancer Progression Scientists showed that up-regulation of nitric oxide synthase (NOS2) occurs in response to hypoxia, serum withdrawal, IFN-γ, and exogenous nitric oxide (NO), consistent with a feed-forward regulation of NO production by the tumor microenvironment in breast cancer biology. [Proc Natl Acad Sci USA] Abstract | Full Article Essential Role for TrpC5-Containing Extracellular Vesicles in Breast Cancer with Chemotherapeutic Resistance In adriamycin-resistant human breast cancer cells (MCF-7/ADM), investigators analyzed the role of transient receptor potential channel 5 (TrpC5) in extracellular vesicles formation and transfer as well as the diagnostic implications. [Proc Natl Acad Sci USA] Abstract Mechanistic Elucidation of the Antitumor Properties of Withaferin A in Breast Cancer Scientists defined activation of extracellular signal-regulated kinase-ribosomal S6 kinase and ETS-like transcription factor 1-CHOP (C-EBP homologous protein) kinase pathways in upregulating transcription of the death receptor 5 (DR5). Through this route, withaferin A acted as an effective DR5 activator capable of potentiating the biologic effects of celecoxib, etoposide, and TRAIL. [Cancer Res] Abstract The Sodium Channel β1 Subunit Mediates Outgrowth of Neurite-Like Processes on Breast Cancer Cells and Promotes Tumor Growth and Metastasis Researchers found that SCN1B mRNA/β1 protein were up-regulated in breast cancer (BCa) specimens, compared with normal breast tissue. β1 up-regulation substantially increased tumor growth and metastasis in a xenograft model of BCa. [Int J Cancer] Abstract | Full Article Retinoic Acid Reduces Migration of Human Breast Cancer Cells: Role of Retinoic Acid Receptor Beta Administration of retinoic acid (RA) in breast cancer cells induced retinoic acid receptor β (RARβ) gene expression that was greatest after 72 hours with a concentration 1 μM. High concentrations of RA increased the expression of RARβ causing an inhibition of the 60% in cell migration and significantly decreased the expression of migration-related proteins. [J Cell Mol Med] Full Article Bisphenol AF-Induced Endogenous Transcription Is Mediated by ERα and ERK1/2 Activation in Human Breast Cancer Cells The authors investigated the effect and mechanism of bisphenol AF (BPAF)-induced endogenous transcription detected by real-time PCR in human breast cancer cells. They found that BPAF stimulated transcription of estrogen responsive genes, such as trefoil factor 1, growth regulation by estrogen in breast cancer 1 and cathepsin D, through dose-dependent and time-dependent manners in T47D and MCF7 cells. [PLoS One] Full Article CLINICAL RESEARCH Phase IIa Trial of Trastuzumab Emtansine with Pertuzumab for Patients with Human Epidermal Growth Factor Receptor 2-Positive, Locally Advanced, or Metastatic Breast Cancer This Phase IIa study characterized the safety and efficacy of two human epidermal growth factor receptor 2 (HER2)-targeted agents, trastuzumab emtansine and pertuzumab, in patients with HER2-positive metastatic breast cancer. [J Clin Oncol] Abstract Randomized Phase II Study of Weekly Paclitaxel with and without Carboplatin followed by Cyclophosphamide/Epirubicin/5-Fluorouracil as Neoadjuvant Chemotherapy for Stage II/IIIA Breast Cancer without HER2 Overexpression Addition of carboplatin to neoadjuvant chemotherapy in HER2-negative breast cancer may improve pathological complete response rates. Investigators evaluated the efficacy and safety of carboplatin and weekly paclitaxel followed by cyclophosphamide, epirubicin, and 5-fluorouracil as neoadjuvant chemotherapy for HER2-negative breast cancer. [Breast Cancer Res Treat] Abstract |