LABORATORY RESEARCH Molecular Profiling of Human Mammary Gland Links Breast Cancer Risk to a p27+ Cell Population with Progenitor Characteristics Researchers characterized the global gene expression and epigenetic profiles of multiple cell types from normal breast tissue of nulliparous and parous women and carriers of BRCA1 or BRCA2 mutations. They found significant differences in CD44+ progenitor cells, where the levels of many stem cell-related genes and pathways, including the cell-cycle regulator p27, are lower in parous women without BRCA1/BRCA2 mutations. [Cell Stem Cell] Abstract | Graphical Abstract Selective Estrogen Receptor Modulators and Pharmacogenomic Variation in ZNF423 Regulation of BRCA1 Expression: Individualized Breast Cancer Prevention An initial discovery genome-wide association study identified common single-nucleotide polymorphisms (SNP) in or near the ZNF423 and CTSO genes that were associated with breast cancer risk during selective estrogen receptor modulators therapy. The authors then showed that both ZNF423 and CTSO participated in the estrogen-dependent induction of BRCA1 expression, in both cases with SNP-dependent variation in induction. [Cancer Discov] Abstract | Press Release CD73 Promotes Anthracycline Resistance and Poor Prognosis in Triple Negative Breast Cancer Using mouse models of breast cancer, scientists demonstrated that CD73 overexpression in tumor cells conferred chemoresistance to doxorubicin, a commonly used anthracycline, by suppressing adaptive antitumor immune responses via activation of A2A adenosine receptors. [Proc Natl Acad Sci USA] Abstract Antioxidant Enzymes Mediate Survival of Breast Cancer Cells Deprived of Extracellular Matrix Investigators report the discovery of a prominent role for antioxidant enzymes, including catalase and superoxide dismutase, in facilitating the survival of breast cancer cells after extracellular matrix (ECM)-detachment. Enhanced expression of antioxidant enzymes in nonmalignant mammary epithelial cells detached from ECM resulted in ATP elevation and survival in the luminal space of mammary acini. [Cancer Res] Abstract The Gene Desert Mammary Carcinoma Susceptibility Locus Mcs1a Regulates Nr2f1 Modifying Mammary Epithelial Cell Differentiation and Proliferation Researchers developed a megadeletion mouse model, which lacks 535 Kb of sequence containing the Mcs1a ortholog. Global gene expression analysis by RNA-seq revealed that in the mouse mammary gland, the orphan nuclear receptor gene Nr2f1/Coup-tf1 is regulated by Mcs1a. In resistant Mcs1a congenic rats, as compared with susceptible congenic control rats, they found Nr2f1 transcript levels to be elevated in mammary gland, epithelial cells, and carcinoma samples. [PLoS Genet] Full Article The Pluripotency Factor Nanog Promotes Breast Cancer Tumorigenesis and Metastasis To elucidate the physiological roles of Nanog in tumorigenesis, the authors developed an inducible Nanog transgenic mouse model, in which the expression of Nanog in adult tissues can be induced via LoxP/Cre-mediated deletion. Their findings indicate that overexpression of Nanog in the mammary gland is not sufficient to induce mammary tumor. However, when coexpressed with Wnt-1 in the mouse mammary gland, it promotes mammary tumorigenesis and metastasis. [Oncogene] Abstract Apoptotic Circulating Tumor Cells (CTCs) in Early and Metastatic Breast Cancer Patients Since it is unclear if all CTCs are capable of generating metastasis, scientists investigated apoptotic and proliferative status in 56 CTC-positive breast cancer patients. Double staining immunofluorescence experiments were performed in peripheral blood mononuclear cells cytospins using the pancytokeratin A45-B/B3 antibody and either M30 or Ki67 antibodies. [Mol Cancer Ther] Abstract miR-181a Enhances Drug Sensitivity in Mitoxantone-Resistant Breast Cancer Cells by Targeting Breast Cancer Resistance Protein (BCRP/ABCG2) The authors investigated the role of microRNAs (miRNAs) in regulation of BCRP expression and BCRP-mediated drug resistance in breast cancer cells. Microarray analysis was performed to determine the differential expression patterns of miRNAs that target BCRP between the MX-resistant breast cancer cell line MCF-7/MX and its parental MX-sensitive cell line MCF-7. [Breast Cancer Res Treat] Abstract CLINICAL RESEARCH Six Months versus 12 Months of Adjuvant Trastuzumab for Patients with HER2-Positive Early Breast Cancer (PHARE): A Randomized Phase III Trial Investigators did an open-label, randomized, phase III trial in 156 centers in France. Patients with HER2-positive early breast cancer who had received at least four cycles of chemotherapy, had breast-axillary surgery, and had received up to six months of trastuzumab before randomization were eligible. [Lancet Oncol] Abstract Capecitabine Plus Paclitaxel versus Epirubicin Plus Paclitaxel as First-Line Treatment for Metastatic Breast Cancer: Efficacy and Safety Results of a Randomized, Phase III Trial by the AGO Breast Cancer Study Group Researchers conducted a randomized, phase III, noninferiority trial comparing capecitabine plus paclitaxel with epirubicin plus paclitaxel as first-line therapy for metastatic breast cancer, regarding progression-free survival as primary efficacy endpoint. [Breast Cancer Res Treat] Abstract |