LABORATORY RESEARCH An Epigenomic Approach to Therapy for Tamoxifen-Resistant Breast Cancer In an effort to identify novel regulators of estrogen receptor alpha (ERα) signaling, through a small-scale siRNA screen against histone methyl modifiers, investigators found WHSC1, a histone H3K36 methyltransferase, as a positive regulator of ERα signaling in breast cancer cells. [Cell Res] Full Article Targeting RPL39 and MLF2 Reduces Tumor Initiation and Metastasis in Breast Cancer by Inhibiting Nitric Oxide Synthase Signaling Selective shRNA knockdown identified ribosomal protein L39 (RPL39) and myeloid leukemia factor 2 (MLF2) as the top candidates that affect breast cancer stem cell (BCSC) self-renewal. Knockdown of RPL39 and MLF2 by specific siRNA nanoparticles in patient-derived and human cancer xenografts reduced tumor volume and lung metastases with a concomitant decrease in BCSCs. [Proc Natl Acad Sci USA] Abstract STAT3 Signaling Is Activated Preferentially in Tumor-Initiating Cells in Claudin-Low Models of Human Breast Cancer Researchers constructed a series of lentiviral fluorescent reporters that enabled flow cytometric enrichment of cells differing in STAT3-mediated transcriptional activity, as well as in vivo/in situ localization of STAT3 responsive cells. [Stem Cells] Abstract Aldehyde Dehydrogenase and Estrogen Receptor Define a Hierarchy of Cellular Differentiation in the Normal Human Mammary Epithelium Investigators used fluorescence activated cell sorting of primary human mammary epithelial cells along with in vitro and in vivo functional assays to examine the hierarchical relationship between cells with aldehyde dehydrogenase enzymatic activity and estrogen receptor positive cells in the normal human breast epithelium. [Breast Cancer Res] Abstract | Full Article Chromatinized PKC-θ Directly Regulates Inducible Genes in Epithelial to Mesenchymal Transition and Breast Cancer Stem Cells Scientists showed that crosstalk between signaling kinases and chromatin is critical for eliciting inducible transcriptional programs that drive mesenchymal differentiation and cancer stem cell formation, providing novel mechanisms to target using epigenetic therapy in breast cancer. [Mol Cell Biol] Abstract Estrogen Promotes Stemness and Invasiveness of ER-Positive Breast Cancer Cells through Gli1 Activation Considering that Gli1, part of the Sonic hedgehog developmental pathway, has been shown to mediate breast cancer (BC) stem cells (CSCs), researchers investigated whether estrogen and Gli1 could promote CSCs and epithelial-mesenchymal transition in estrogen receptor positive (ER+) BC cell lines. [Mol Cancer] Abstract | Full Article Growth Hormone Is Secreted by Normal Breast Epithelium upon Progesterone Stimulation and Increases Proliferation of Stem/Progenitor Cells Using in vitro and in vivo experimental systems and in situ analysis, scientists showed that growth hormone is secreted locally by normal human mammary epithelial cells upon progesterone stimulation. [Stem Cell Rep] Full Article | Graphical Abstract CLINICAL RESEARCH Distant Invasive Breast Cancer Recurrence Risk in Human Epidermal Growth Factor Receptor 2-Positive T1a and T1b Node-Negative Localized Breast Cancer Diagnosed from 2000 to 2006: A Cohort from an Integrated Health Care Delivery System Investigators determined the invasive recurrence risk among patients with small, node-negative human epidermal growth factor receptor 2-positive breast cancer. [J Clin Oncol] Abstract | Press Release A Multi-Institutional Study on the Association between BRCA1/BRCA2 Mutational Status and Triple-Negative Breast Cancer in Familial Breast Cancer Patients Researchers studied 221 familial breast and/or ovarian cancer patients from 37 hospitals using a comprehensive approach to identify large genomic rearrangements as well as sequence variants, and investigated the association between BRCA1/2 mutational status and triple-negative breast cancer. [Breast Cancer Res Treat] Abstract |