LABORATORY RESEARCH Circulating Breast Tumor Cells Exhibit Dynamic Changes in Epithelial and Mesenchymal Composition Epithelial-mesenchymal transition (EMT) of adherent epithelial cells to a migratory mesenchymal state has been implicated in tumor metastasis in preclinical models. To investigate its role in human cancer, scientists characterized EMT in circulating tumor cells from breast cancer patients. [Science] Abstract | Press Release Preclinical Therapy of Disseminated HER-2+ Ovarian and Breast Carcinomas with a HER-2-Retargeted Oncolytic Herpesvirus Investigators retargeted herpes simplex virus tropism to HER-2 oncoprotein p185, overexpressed in ovary and breast cancers. The HER-2-retargeted R-LM249 exclusively infects and kills tumor cells expressing high levels of human HER-2. [PLoS Pathol] Full Article MicroRNA-7 Suppresses Brain Metastasis of Breast Cancer Stem-Like Cells by Modulating KLF4 Cancer stem-like cells (CSCs) are considered to play a role in metastatic progression of breast cancer; however, the exact pathologic role of CSCs is yet to be elucidated. Researchers found that CSCs (CD24−/CD44+/ESA+) isolated from metastatic breast cell lines are significantly more metastatic than non-CSC populations in an organ-specific manner. [Cancer Res] Abstract | Press Release FOXC2 Expression Links Epithelial-Mesenchymal Transition and Stem Cell Properties in Breast Cancer Scientists report that the transcription factor FOXC2 induced in response to multiple epithelial-mesenchymal transition (EMT) signaling pathways as well as elevated in stem cell-enriched factions is a critical determinant of mesenchymal and stem cell properties, in cells induced to undergo EMT and cancer stem cell-enriched breast cancer cell lines. [Cancer Res] Abstract Ink4a/Arf−/− and HRAS(G12V) Transform Mouse Mammary Cells into Triple-Negative Breast Cancer Containing Tumorigenic CD49f− Quiescent Cells Investigators proposed to engineer a mouse mammary tumor model with intratumoral heterogeneity by using defined genetic perturbations. To achieve this, they used mice with knockout (-/-) of Ink4a/Arf, a tumor suppressor locus; these mice are known to be susceptible to non-mammary tumors such as fibrosarcoma. [Oncogene] Abstract Microfabricated Collagen Tracks Facilitate Single Cell Metastatic Invasion in 3D Studies have shown that some cancer cells can use proteolysis to mechanically rearrange their extracellular matrix to form tube-like “microtracks” which other cells can follow without using matrix metalloproteinases themselves. The authors speculate that this mode of migration in the secondary cells may be one example of migration which can occur without endogenous protease activity in the secondary cells. They present a technique to study this migration in a 3D, collagen-based environment which mimics the size and topography of the tracks produced by proteolytically active cancer cells. [Integrative Biol] Abstract The HER2- and Heregulin β1 (HRG)-Inducible TNFR Superfamily Member Fn14 Promotes HRG-Driven Cell Migration, Invasion and Matrix Metalloproteinase-9 Expression In a previous study, the authors found that fibroblast growth factor-inducible 14 (Fn14), a member of the TNF receptor (TNFR) superfamily, was frequently overexpressed in human epidermal growth factor receptor-2 (HER2)+ breast tumors. They report here that HER2 and Fn14 are also co-expressed in mammary tumors that develop in two different transgenic mouse models of breast cancer. [Mol Cancer Res] Abstract Peroxisome Proliferator Activated Receptor-α/Hypoxia Inducible Factor-1α Interplay Sustains Carbonic Anhydrase IX and Apoliprotein E Expression in Breast Cancer Stem Cells The authors report on the relationship between nuclear receptors activity and the modulation of the pro-inflammatory phenotype in breast cancer stem cells. [PLoS One] Full Article CLINICAL RESEARCH Phase II Randomized Study of Trastuzumab Emtansine versus Trastuzumab Plus Docetaxel in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer Patients with human epidermal growth factor receptor 2-positive metastatic breast cancer or recurrent locally advanced breast cancer were randomly assigned to trastuzumab plus docetaxel or trastuzumab emtansine as first-line treatment until disease progression or unacceptable toxicity. [J Clin Oncol] Abstract Multicenter Phase II Trial of Bevacizumab Combined with Docetaxel-Carboplatin for the Neoadjuvant Treatment of Triple-Negative Breast Cancer (KCSG BR-0905) Women with hormone receptor- and human epidermal growth factor receptor 2-negative, stage II/III breast cancer received six cycles of docetaxel, carboplatin and bevacizumab every 21 days. [Ann Oncol] Abstract |