LABORATORY RESEARCH Injectable Hydrogels from Triblock Copolymers of Vitamin E-Functionalized Polycarbonate and Poly(ethylene glycol) for Subcutaneous Delivery of Antibodies for Cancer Therapy Results demonstrated that Herceptin-loaded hydrogel is specific towards HER2-overexpressing cancer cells and cytotoxic action is comparable to that of Herceptin solution. The biocompatibility and biodegradability of hydrogel were evaluated in mice with subcutaneous injection by histological examination. [Adv Funct Mater] Abstract | Press Release Mitochondrial Retrograde Signaling Induces Epithelial-Mesenchymal Transition and Generates Breast Cancer Stem Cells Investigators demonstrated that reducing mitochondrial DNA content in human mammary epithelial cells activates the Calcineurin-dependent mitochondrial retrograde signaling pathway, which induces epithelial-to-mesenchymal transition-like reprogramming to fibroblastic morphology, loss of cell polarity, contact inhibition and acquired migratory and invasive phenotype. [Oncogene] Abstract | Press Release Inhibition of c-Src Blocks Estrogen-Induced Apoptosis and Restores Estrogen-Stimulated Growth in Long-Term Estrogen-Deprived Breast Cancer Cells To mimic the clinical administration of c-Src inhibitors, the authors treated cells with either estrogen (E2), a c-Src inhibitor PP2, or the combination for 8 weeks to explore the apoptotic potential of the c-Src inhibitor and E2 on MCF-7:5C cells. [Eur J Cancer] Abstract Myc Is Required for β-Catenin-Mediated Mammary Stem Cell Amplification and Tumorigenesis Microarray analysis was used to compare K5ΔNβcat mouse tumors to human breast tumors, mammary cancer cell lines and the tumors developed in other mouse models. Cre-Lox approach was employed to delete Myc from the mammary basal cell layer of K5ΔNβcat mice. Stem cell amplification in K5ΔNβcat mouse mammary epithelium was assessed with 3D-culture and transplantation assays. [Mol Cancer] Full Article The Insulin Receptor Plays an Important Role in Secretory Differentiation in the Mammary Gland In an acinar preparation from mammary epithelial cells isolated from pregnant mice, insulin stimulated lumen formation, mammary cell size, acinar size, acinar casein content, and the formation of lipid droplets with a Km of ~1.7 nM. IGF-I and IGF-II had no effect at concentrations below 50 nM, and a function blocking antibody to the IGF type 1 receptor did not alter the response to insulin. [Am J Physiol-Endocrinol Metab] Abstract RAGE-Binding S100A8/A9 Promotes the Migration and Invasion of Human Breast Cancer Cells through Actin Polymerization and Epithelial-Mesenchymal Transition Researchers report for the first time that S100A8/A9 promoted the invasion of breast cancer cells depending on receptor for advanced glycation end products (RAGE). In addition, RAGE binding to S100A8/A9 promoted the phosphorylation of LIN-11, Isl1, and MEC-3 protein domain kinase, as well as cofilin. This phosphorylation is a critical step in cofilin recycling and actin polymerization. [Breast Cancer Res Treat] Abstract 27-Hydroxycholesterol Promotes Cell-Autonomous, ER-Positive Breast Cancer Growth Investigators report that the cholesterol metabolite 27-hydroxycholesterol (27HC) stimulates MCF-7 cell xenograft growth in mice. More importantly, in estrogen receptor (ER)+ breast cancer patients, 27HC content in normal breast tissue was increased compared to that in cancer-free controls, and tumor 27HC content was further elevated. [Cell Rep] Abstract | Graphical Abstract | Press Release CLINICAL RESEARCH Lapatinib as a Component of Neoadjuvant Therapy for HER2-Positive Operable Breast Cancer: An Open-Label, Randomized Phase III Trial The authors studied the effect on tumor response to neoadjuvant therapy of the substitution of lapatinib for trastuzumab in combination with weekly paclitaxel after doxorubicin plus cyclophosphamide treatment, and of the addition of lapatinib and trastuzumab combined after doxorubicin plus cyclophosphamide treatment in patients with HER2-positive operable breast cancer to determine whether there would be a benefit of dual HER2 blockade in these patients. [Lancet Oncol] Abstract Phase II Randomized Trial of Weekly and Every-3-Week Ixabepilone in Metastatic Breast Cancer Patients This multicenter, open-label, randomized phase II trial compared the efficacy and tolerability of weekly ixabepilone versus the standard 3 weekly dosing regimen. Patients with human epidermal growth factor receptor 2-negative, metastatic breast cancer were randomly assigned to receive either ixabepilone 16 mg/m2 as a 1-hour intravenous (IV) infusion weekly on days 1, 8, and 15 of a 28-day cycle, or 40 mg/m2 as a 3-hour IV infusion on day 1 of a 21-day cycle, until disease progression or unacceptable toxicity. [Breast Cancer Res Treat] Abstract |