LABORATORY RESEARCH Progesterone Drives Mammary Secretory Differentiation via RankL-Mediated Induction of Elf5 in Luminal Progenitor Cells Progesterone-RankL paracrine signaling has been proposed as a driver of stem cell expansion in the mammary gland, and Elf5 is essential for the differentiation of mammary epithelial progenitor cells. Scientists demonstrated that Elf5 expression is induced by progesterone and that Elf5 and progesterone cooperate to promote alveolar development. [Development] Abstract AXL Induces Epithelial-to-Mesenchymal Transition and Regulates the Function of Breast Cancer Stem Cells Researchers demonstrated a novel function of AXL in acting upstream to induce epithelial-to-mesenchymal transition in normal and immortalized human mammary epithelial cells in an apparent positive feedback loop mechanism and regulate breast cancer stem cells self-renewal and chemoresistance. [Oncogene] Abstract Protein Kinase Cδ Is Required for ErbB2-Driven Mammary Gland Tumorigenesis and Negatively Correlates with Prognosis in Human Breast Cancer The authors present in-vivo evidence that protein kinase C δ (PKCδ) is essential for the development of mammary gland tumors in a ErbB2-overexpressing transgenic mouse model, and in-vitro evidence that PKCδ is required for proliferative signaling downstream of the ErbB2 receptor. [Oncogene] Abstract Cucurbitacin I Inhibits Rac1 Activation in Breast Cancer Cells by a Reactive Oxygen Species-Mediated Mechanism and Independently of Jak2 and P-Rex1 As the Jak2/Stat3 pathway has been shown to be functionally associated with ErbB receptors, scientists asked if this pathway could mediate P-Rex1/Rac1 activation in response to ErbB ligands. [Mol Pharmacol] Abstract Micro-RNA-584 and the Protein Phosphatase and Actin Regulator 1 (PHACTR1): New Signaling Route through which Transforming Growth Factor-Beta Mediates the Migration and Actin Dynamics of Breast Cancer Cells The authors found TGF-beta to down-regulate the expression of mircoRNA (miR)-584 in breast cancer cells. Furthermore, they identified PHACTR1, an actin-binding protein, to be positively regulated by TGF-beta in a miR-584-dependent manner. [J Biol Chem] Abstract Naïve Rat Umbilical Cord Matrix Stem Cells Significantly Attenuate Mammary Tumor Growth through Modulation of Endogenous Immune Responses The possible mechanisms of tumor growth attenuation by rat umbilical cord matrix stem cells were studied using orthotopic Mat B III rat mammary tumor grafts in female F344 rats. [Cytotherapy] Abstract AMR-Me Inhibits PI3K/Akt Signaling in Hormone-Dependent MCF-7 Breast Cancer Cells and Inactivates NF-κB in Hormone-Independent MDA-MB-231 Cells Scientists showed that AMR-Me dose-dependently inhibited the proliferation of MCF-7 and MDA-MB-231 cells under serum-free conditions supplemented with 1nM estrogen with an IC50 value of 0.15µM, 0.45µM, respectively. [Mol Carcinog] Abstract CLINICAL RESEARCH Phase II Study of Paclitaxel, Trastuzumab, and Lapatinib as Adjuvant Therapy for Early Stage HER2-Positive Breast Cancer In a single-arm Phase II study, patients with stages I-III HER2-positive breast cancer received standard anthracycline-based chemotherapy followed by weekly taxane, with concurrent standard trastuzumab, plus daily lapatinib for a total of 12 months. [Breast Cancer Res Treat] Abstract | Full Article Cardiac Tolerability of Pertuzumab plus Trastuzumab plus Docetaxel in Patients with HER2-Positive Metastatic Breast Cancer in CLEOPATRA: A Randomized, Double-Blind, Placebo-Controlled Phase III Study The authors report cardiac tolerability of pertuzumab plus trastuzumab plus docetaxel versus placebo plus trastuzumab plus docetaxel observed in the Phase III study CLEOPATRA in patients with HER2-positive first-line metastatic breast cancer. [Oncologist] Abstract |