LABORATORY RESEARCH Tyrosine Phosphatase SHP2 Promotes Breast Cancer Progression and Maintains Tumor-Initiating Cells via Activation of Key Transcription Factors and a Positive Feedback Signaling Loop New cancer therapies are likely to arise from an in-depth understanding of the signaling networks influencing tumor initiation, progression and metastasis. Researchers show a fundamental role for Src-homology 2 domain-containing phosphatase 2 (SHP2) in these processes in human epidermal growth factor receptor 2-positive and triple-negative breast cancers. [Nat Med] Abstract | Press Release ErbB-2 Signals through Plexin-B1 to Promote Breast Cancer Metastasis Investigators show that overexpression of ErbB-2 in human breast cancer cell lines leads to phosphorylation and activation of the semaphorin receptor Plexin-B1. [J Clin Invest] Abstract | Press Release Estrogen Receptor Alpha Mediates Progestin-Induced Mammary Tumor Growth by Interacting with Progesterone Receptors at the Cyclin D1/MYC Promoters In this study, scientists used a murine progestin-dependent tumor to investigate the role of estrogen receptor alpha in progestin-induced tumor cell proliferation. [Cancer Res] Abstract Impact of Intertumoral Heterogeneity on Predicting Chemotherapy Response of BRCA1-Deficient Mammary Tumors Researchers searched for gene expression patterns that correlate with docetaxel or cisplatin response in a mouse model for breast cancer associated with BRCA1 deficiency. [Cancer Res] Abstract P-Cadherin Is Co-Expressed with Cd44 and Cd49f and Mediates Stem Cell Properties in Basal-Like Breast Cancer The aim of this study was to test whether P-cadherin mediates stem cell properties in basal-like breast carcinomas. [Stem Cells] Abstract Akt and ERK Control the Proliferative Response of Mammary Epithelial Cells to the Growth Factors IGF-1 and EGF through the Cell Cycle Inhibitor p57Kip2 Using high-content immunofluorescence microscopy, scientists quantitated differences in signaling networks downstream of epidermal growth factor (EGF), which stimulated proliferation of mammary epithelial cells, and insulin or insulin-like growth factor 1 (IGF-1), which enhanced the proliferative response to EGF but did not stimulate proliferation independently. [Sci Signal] Abstract ROR1 Is Expressed in Human Breast Cancer and Associated with Enhanced Tumor-Cell Growth Here researchers show that the neoplastic cells of many human breast cancers express the receptor-tyrosine-kinase-like orphan receptor 1 (ROR1) protein and high-level expression of ROR1 in breast adenocarcinoma was associated with aggressive disease. [PLoS One] Abstract | Press Release Stem Cell-Related Markers in Primary Breast Cancers and Associated Metastatic Lesions Investigators hypothesized that stem cell subpopulations would be more frequent in metastatic than in primary tumors. Therefore they assessed by immunohistochemical analysis, tissue microarrays containing tissue from primary and associated metastatic breast cancers for expression of CD24, CD44, E-cadherin and vimentin to evaluate candidate cancer-initiating cell populations in breast cancer subtypes and metastatic lesions. [Mod Pathol] Abstract CLINICAL RESEARCH Pertuzumab Monotherapy After Trastuzumab-Based Treatment and Subsequent Reintroduction of Trastuzumab: Activity and Tolerability in Patients with Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer Scientists recruited a third cohort of patients who received pertuzumab without trastuzumab. They then investigated the impact of reintroducing trastuzumab to patients whose disease progressed on pertuzumab monotherapy. [J Clin Oncol] Abstract | Press Release Adjuvant Tamoxifen Reduces Subsequent Breast Cancer in Women with Estrogen Receptor-Positive Ductal Carcinoma In Situ: A Study Based on NSABP Protocol B-24 The NSABP (National Surgical Adjuvant Breast and Bowel Project) B-24 study demonstrated significant benefit with adjuvant tamoxifen in patients with ductal carcinoma in situ after lumpectomy and radiation. The current study retrospectively evaluated the relationship between receptors and response to tamoxifen. [J Clin Oncol] Abstract Conjugated Equine Estrogen and Breast Cancer Incidence and Mortality in Postmenopausal Women with Hysterectomy: Extended Follow-Up of the Women’s Health Initiative Randomized Placebo-Controlled Trial Investigators aimed to assess the influence of estrogen use on longer term breast cancer incidence and mortality in extended follow-up of the women in the Women’s Health Initiative trial. [Lancet Oncol] Abstract | Press Release Neoadjuvant Bevacizumab, Trastuzumab, and Chemotherapy for Primary Inflammatory HER2-Positive Breast Cancer (BEVERLY-2): An Open-Label, Single-Arm Phase II Study In this Phase II trial, scientists aimed to assess efficacy and safety of neoadjuvant bevacizumab combined with trastuzumab and chemotherapy in patients with primary HER2-positive inflammatory breast cancer. [Lancet Oncol] Abstract CYP2D6 Genotype and Tamoxifen Response in Postmenopausal Women with Endocrine-Responsive Breast Cancer: The Breast International Group 1-98 Trial Cytochrome P450 2D6 (CYP2D6) enzyme metabolizes tamoxifen to clinically active metabolites, and CYP2D6 polymorphisms may adversely affect tamoxifen efficacy. In this study, researchers investigated the clinical relevance of CYP2D6 polymorphisms. [J Natl Cancer Inst] Abstract |