LABORATORY RESEARCH A Renewable Tissue Resource of Phenotypically Stable, Biologically and Ethnically Diverse, Patient-Derived Human Breast Cancer Xenografts Breast cancer research is hampered by difficulties in obtaining and studying primary human breast tissue, and by the lack of in vivo preclinical models that reflect patient tumor biology accurately. To overcome these limitations, scientists propagated a cohort of human breast tumors grown in the epithelium-free mammary fat pad of SCID/Beige and NOD/SCID/IL2γ-receptor null mice, under a series of transplant conditions. [Cancer Res] Abstract Targeting Treatment Resistant Breast Cancer Stem Cells with FKBPL and Its Peptide Derivative, AD-01, via the CD44 Pathway Researchers explored the ability of AD-01 to target CD44 positive breast cancer stem cells (BCSCs). Mammosphere assays and flow cytometry were utilized to analyze the effect of FKBPL overexpression/knockdown and AD-01 treatment ± other anti-cancer agents on BCSCs using breast cancer cell lines, primary patient samples and xenografts. [Clin Cancer Res] Abstract Prolactin Suppresses a Progestin-Induced CK5-Positive Cell Population in Luminal Breast Cancer through Inhibition of Progestin-Driven BCL6 Expression Investigators report that prolactin counteracts induction of the cytokeratin-5 (CK5)-positive population by the synthetic progestin R5020 in luminal breast cancer cells both in vitro and in vivo. [Oncogene] Abstract Deficiency of Kruppel-Like Factor KLF4 in Mammary Tumor Cells Inhibits Tumor Growth and Pulmonary Metastasis and Is Accompanied by Compromised Recruitment of Myeloid-Derived Suppressor Cells By using a spontaneously metastatic 4T1 breast cancer mouse model and an immunodeficient NOD/SCID mouse model, the authors demonstrated that KLF4 knockdown delayed tumor development and inhibited pulmonary metastasis, which was accompanied by decreased accumulation of myeloid-derived suppressor cells in bone marrow, spleens and primary tumors. [Int J Cancer] Abstract TLR4 Ligand/H2O2 Enhances TGF-β1 Signaling to Induce Metastatic Potential of Non-Invasive Breast Cancer Cells by Activating Non-Smad Pathways Scientists report that the enhancement of TGF-β1 signaling is required for inducing metastatic potential of non-invasive breast cancer cells. TGF-β1 alone could not efficiently induce the sustained activation of Smad and non-Smad pathways in non-invasive breast cancer cells. TLR4 ligand and H2O2 cooperated with TGF-β1 to enhance the sustained activation of non-Smad pathways, including p38MAPK, ERK, JNK, PI3K, and NF-κB. [PLoS One] Full Article In Vitro Analysis of Breast Cancer Cell Line Tumourspheres and Primary Human Breast Epithelia Mammospheres Demonstrates Inter- and Intrasphere Heterogeneity Investigators surveyed sphere-forming capacity across 26 breast cell lines, immunophenotyped spheres from six luminal- and basal-like lines by immunohistochemistry and flow cytometry and compared clonogenicity between sphere, adherent and matrigel culture formats using in vitro functional assays. [PLoS One] Full Article | Press Release Molecular Genetic Analysis of VRK1 in Mammary Epithelial Cells: Depletion Slows Proliferation In Vitro and Tumor Growth and Metastasis In Vivo The authors investigated the role of vaccinia-related kinase 1 (VRK1) in the growth of normal and malignant human mammary epithelial cells, and demonstrated that shRNA-mediated depletion of VRK1 slows their proliferation significantly. [Oncogenesis] Full Article The Luminal Progenitor Compartment of the Normal Human Mammary Gland Constitutes a Unique Site of Telomere Dysfunction Telomeres are essential for genomic integrity, but little is known about their regulation in the normal human mammary gland. The authors demonstrated that a phenotypically defined cell population enriched in luminal progenitors is characterized by unusually short telomeres independently of donor age. [Stem Cell Rep] Abstract | Press Release CLINICAL RESEARCH Randomized Phase II Study of the Anti–Epidermal Growth Factor Receptor Monoclonal Antibody Cetuximab with Cisplatin versus Cisplatin Alone in Patients with Metastatic Triple-Negative Breast Cancer Epidermal growth factor receptor is overexpressed in metastatic triple-negative breast cancers, an aggressive subtype of breast cancer. The authors’ randomized phase II study investigated cisplatin with or without cetuximab in this setting. Patients who had received no more than one previous chemotherapy regimen were randomly assigned on a 2:1 schedule to receive no more than six cycles of cisplatin plus cetuximab or cisplatin alone. [J Clin Oncol] Abstract Prospective Observational Study of Breast Cancer Treatment Outcomes for UK Women Aged 18-40 Years at Diagnosis: The POSH Study Between 2000 and 2008, 2956 patients aged 40 years or younger were recruited to a UK multicenter prospective observational cohort study (POSH). Details of tumor pathology, disease stage, treatment received, and outcome were recorded. Overall survival and distant disease-free interval were assessed using Kaplan-Meier curves. [J Natl Cancer Inst] Abstract | Press Release |