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    Selective serotonin reuptake inhibitor use and breast cancer survival: a population-based cohort study.
    Breast Cancer Res 2018 Jan 19;20(1). Epub 2018 Jan 19.
    Centre for Public Health, Queen's University Belfast, Belfast, UK.
    Background: Nearly 50% of breast cancer patients suffer from depression or anxiety. Selective serotonin reuptake inhibitors (SSRIs), the first-line pharmacological treatment for depression, have been implicated in breast cancer development through increased prolactin levels and tamoxifen metabolism inhibition. Previous studies of breast cancer progression have focused on tamoxifen users, or have been limited by their small sample size and methodology. Read More

    Evaluating the breast cancer predisposition role of rare variants in genes associated with low-penetrance breast cancer risk SNPs.
    Breast Cancer Res 2018 Jan 9;20(1). Epub 2018 Jan 9.
    Cancer Genetics Laboratory, Research Division, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC, 3000, Australia.
    Background: Genome-wide association studies (GWASs) have identified numerous single-nucleotide polymorphisms (SNPs) associated with small increases in breast cancer risk. Studies to date suggest that some SNPs alter the expression of the associated genes, which potentially mediates risk modification. On this basis, we hypothesised that some of these genes may be enriched for rare coding variants associated with a higher breast cancer risk. Read More

    SNPs related to vitamin D and breast cancer risk: a case-control study.
    Breast Cancer Res 2018 Jan 2;20(1). Epub 2018 Jan 2.
    Department of Surgery, Lund University, Skåne University Hospital, SE-205 02, Malmö, Sweden.
    Background: It has been suggested that vitamin D might protect from breast cancer, although studies on levels of vitamin D in association with breast cancer have been inconsistent. Genome-wide association studies (GWASs) have identified several single-nucleotide polymorphisms (SNPs) to be associated with vitamin D. The aim of this study was to investigate such vitamin D-SNP associations in relation to subsequent breast cancer risk. Read More

    Identifying biomarkers of breast cancer micrometastatic disease in bone marrow using a patient-derived xenograft mouse model.
    Breast Cancer Res 2018 Jan 2;20(1). Epub 2018 Jan 2.
    Department of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO, 63110, USA.
    Background: Disseminated tumor cells (DTCs) found in the bone marrow (BM) of patients with breast cancer portend a poor prognosis and are thought to be intermediaries in the metastatic process. To assess the clinical relevance of a mouse model for identifying possible prognostic and predictive biomarkers of these cells, we have employed patient-derived xenografts (PDX) for propagating and molecularly profiling human DTCs.

    Methods: Previously developed mouse xenografts from five breast cancer patients were further passaged by implantation into NOD/SCID mouse mammary fat pads. Read More

    Use of prescription drugs and risk of postoperative red blood cell transfusion in breast cancer patients: a Danish population-based cohort study.
    Breast Cancer Res 2017 Dec 22;19(1):135. Epub 2017 Dec 22.
    Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200, Aarhus N, Denmark.
    Background: Several frequently used prescription drugs may affect bleeding risk. We investigated use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), selective serotonin reuptake inhibitors (SSRIs), and statins and risk of postoperative red blood cell transfusion in breast cancer patients.

    Methods: Using Danish population-based registries, we identified a cohort of women who underwent surgery for primary breast cancer (n = 22,238) during 2005-2012 and ascertained their use of aspirin, NSAIDs, SSRIs, and statins. Read More

    miR-105/93-3p promotes chemoresistance and circulating miR-105/93-3p acts as a diagnostic biomarker for triple negative breast cancer.
    Breast Cancer Res 2017 Dec 19;19(1):133. Epub 2017 Dec 19.
    Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
    Background: Triple negative breast cancer (TNBC) lacks both early detection biomarkers and viable targeted therapeutics. Moreover, chemotherapy only produces 20-30% pathologic complete response. Because miRNAs are frequently dysregulated in breast cancer and have broad tissue effects, individual or combinations of circulating miRNAs may serve as ideal diagnostic, predictive or prognostic biomarkers, as well as therapeutic targets. Read More

    Association between mammographic breast density and histologic features of benign breast disease.
    Breast Cancer Res 2017 Dec 19;19(1):134. Epub 2017 Dec 19.
    Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester, MN, USA.
    Background: Over 40% of women undergoing breast screening have mammographically dense breasts. Elevated mammographic breast density (MBD) is an established breast cancer risk factor and is known to mask tumors within the dense tissue. However, the association of MBD with high risk benign breast disease (BBD) is unknown. Read More

    Phosphoproteomics reveals network rewiring to a pro-adhesion state in annexin-1-deficient mammary epithelial cells.
    Breast Cancer Res 2017 Dec 12;19(1):132. Epub 2017 Dec 12.
    Translational Biomedical Proteomics, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 61 Biopolis Drive, Singapore, 138673, Singapore.
    Background: Annexin-1 (ANXA1) plays pivotal roles in regulating various physiological processes including inflammation, proliferation and apoptosis, and deregulation of ANXA1 functions has been associated with tumorigenesis and metastasis events in several types of cancer. Though ANXA1 levels correlate with breast cancer disease status and outcome, its distinct functional involvement in breast cancer initiation and progression remains unclear. We hypothesized that ANXA1-responsive kinase signaling alteration and associated phosphorylation signaling underlie early events in breast cancer initiation events and hence profiled ANXA1-dependent phosphorylation changes in mammary gland epithelial cells. Read More

    Race-associated biological differences among luminal A and basal-like breast cancers in the Carolina Breast Cancer Study.
    Breast Cancer Res 2017 Dec 11;19(1):131. Epub 2017 Dec 11.
    Department of Epidemiology, University of North Carolina at Chapel Hill, Campus Box 7435, Chapel Hill, NC, 27599, USA.
    Background: We examined racial differences in the expression of eight genes and their associations with risk of recurrence among 478 white and 495 black women who participated in the Carolina Breast Cancer Study Phase 3.

    Methods: Breast tumor samples were analyzed for PAM50 subtype and for eight genes previously found to be differentially expressed by race and associated with breast cancer survival: ACOX2, MUC1, FAM177A1, GSTT2, PSPH, PSPHL, SQLE, and TYMS. The expression of these genes according to race was assessed using linear regression and each gene was evaluated in association with recurrence using Cox regression. Read More

    Establishing and characterizing patient-derived xenografts using pre-chemotherapy percutaneous biopsy and post-chemotherapy surgical samples from a prospective neoadjuvant breast cancer study.
    Breast Cancer Res 2017 Dec 6;19(1):130. Epub 2017 Dec 6.
    Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
    Background: Patient-derived xenografts (PDXs) are increasingly used in cancer research as a tool to inform cancer biology and drug response. Most available breast cancer PDXs have been generated in the metastatic setting. However, in the setting of operable breast cancer, PDX models both sensitive and resistant to chemotherapy are needed for drug development and prospective data are lacking regarding the clinical and molecular characteristics associated with PDX take rate in this setting. Read More

    GPER mediates the angiocrine actions induced by IGF1 through the HIF-1α/VEGF pathway in the breast tumor microenvironment.
    Breast Cancer Res 2017 Dec 6;19(1):129. Epub 2017 Dec 6.
    Breast Cancer Now Research Unit, Division of Cancer Sciences, Manchester Cancer Research Centre, University of Manchester, Wilmslow Road, Manchester, M204GJ, UK.
    Background: The G protein estrogen receptor GPER/GPR30 mediates estrogen action in breast cancer cells as well as in breast cancer-associated fibroblasts (CAFs), which are key components of microenvironment driving tumor progression. GPER is a transcriptional target of hypoxia inducible factor 1 alpha (HIF-1α) and activates VEGF expression and angiogenesis in hypoxic breast tumor microenvironment. Furthermore, IGF1/IGF1R signaling, which has angiogenic effects, has been shown to activate GPER in breast cancer cells. Read More

    Obesity reversibly depletes the basal cell population and enhances mammary epithelial cell estrogen receptor alpha expression and progenitor activity.
    Breast Cancer Res 2017 Nov 29;19(1):128. Epub 2017 Nov 29.
    Program in Cellular and Molecular Biology, University of Wisconsin-Madison, 1525 Linden Drive, Madison, WI, 53706, USA.
    Background: Obesity is correlated with an increased risk for developing postmenopausal breast cancer. Since obesity rates continue to rise worldwide, it is important to understand how the obese microenvironment influences normal mammary tissue to increase breast cancer risk. We hypothesized that obesity increases the proportion of luminal progenitor cells, which are thought to be the cells of origin for the most common types of breast cancer, potentially leading to an increased risk for breast cancer. Read More

    Serum concentrations of active tamoxifen metabolites predict long-term survival in adjuvantly treated breast cancer patients.
    Breast Cancer Res 2017 Nov 28;19(1):125. Epub 2017 Nov 28.
    Department of Clinical Science, University of Bergen, Bergen, Norway.
    Background: Controversies exist as to whether the genetic polymorphisms of the enzymes responsible for the metabolism of tamoxifen can predict breast cancer outcome in patients using adjuvant tamoxifen. Direct measurement of concentrations of active tamoxifen metabolites in serum may be a more biological plausible and robust approach. We have investigated the association between CYP2D6 genotypes, serum concentrations of active tamoxifen metabolites, and long-term outcome in tamoxifen treated breast cancer patients. Read More

    Nanopore sequencing of full-length BRCA1 mRNA transcripts reveals co-occurrence of known exon skipping events.
    Breast Cancer Res 2017 Nov 28;19(1):127. Epub 2017 Nov 28.
    Department of Pathology, University of Otago, Christchurch, New Zealand.
    Background: Laboratory assays evaluating the effect of DNA sequence variants on BRCA1 mRNA splicing may contribute to classification by providing molecular evidence. However, our knowledge of normal and aberrant BRCA1 splicing events to date has been limited to data derived from assays targeting partial transcript sequences. This study explored the utility of nanopore sequencing to examine whole BRCA1 mRNA transcripts and to provide accurate categorisation of in-frame and out-of-frame splicing events. Read More

    Influence of breast compression pressure on the performance of population-based mammography screening.
    Breast Cancer Res 2017 Nov 28;19(1):126. Epub 2017 Nov 28.
    Department of Radiology and Nuclear Medicine, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
    Background: In mammography, breast compression is applied to reduce the thickness of the breast. While it is widely accepted that firm breast compression is needed to ensure acceptable image quality, guidelines remain vague about how much compression should be applied during mammogram acquisition. A quantitative parameter indicating the desirable amount of compression is not available. Read More

    Residential particulate matter and distance to roadways in relation to mammographic density: results from the Nurses' Health Studies.
    Breast Cancer Res 2017 Nov 23;19(1):124. Epub 2017 Nov 23.
    Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
    Background: High mammographic density is a strong, well-established breast cancer risk factor. Three studies conducted in various smaller geographic settings reported inconsistent findings between air pollution and mammographic density. We assessed whether particulate matter (PM) exposures (PM2. Read More

    Smoking and risk of breast cancer in the Generations Study cohort.
    Breast Cancer Res 2017 Nov 22;19(1):118. Epub 2017 Nov 22.
    Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
    Background: Plausible biological reasons exist regarding why smoking could affect breast cancer risk, but epidemiological evidence is inconsistent.

    Methods: We used serial questionnaire information from the Generations Study cohort (United Kingdom) to estimate HRs for breast cancer in relation to smoking adjusted for potentially confounding factors, including alcohol intake.

    Results: Among 102,927 women recruited 2003-2013, with an average of 7. Read More

    Serum thymidine kinase 1 activity as a pharmacodynamic marker of cyclin-dependent kinase 4/6 inhibition in patients with early-stage breast cancer receiving neoadjuvant palbociclib.
    Breast Cancer Res 2017 Nov 21;19(1):123. Epub 2017 Nov 21.
    Division of Oncology, Section of Medical Oncology, Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO, 63110, USA.
    Background: Thymidine kinase 1 (TK1) is a cell cycle-regulated enzyme with peak expression in the S phase during DNA synthesis, and it is an attractive biomarker of cell proliferation. Serum TK1 activity has demonstrated prognostic value in patients with early-stage breast cancer. Because cyclin-dependent kinase 4/6 (CDK4/6) inhibitors prevent G1/S transition, we hypothesized that serum TK1 could be a biomarker for CDK4/6 inhibitors. Read More

    The endonuclease EEPD1 mediates synthetic lethality in RAD52-depleted BRCA1 mutant breast cancer cells.
    Breast Cancer Res 2017 Nov 16;19(1):122. Epub 2017 Nov 16.
    Department of Medicine and the Cancer Center, University of Florida Health, 1600 SW Archer Rd, Gainesville, FL, 32610, USA.
    Background: Proper repair and restart of stressed replication forks requires intact homologous recombination (HR). HR at stressed replication forks can be initiated by the 5' endonuclease EEPD1, which cleaves the stalled replication fork. Inherited or acquired defects in HR, such as mutations in breast cancer susceptibility protein-1 (BRCA1) or BRCA2, predispose to cancer, including breast and ovarian cancers. Read More

    Local estrogen axis in the human bone microenvironment regulates estrogen receptor-positive breast cancer cells.
    Breast Cancer Res 2017 Nov 15;19(1):121. Epub 2017 Nov 15.
    Department of Pediatrics, Stanford University School of Medicine, 150E Clark Center, 318 Campus Drive, Stanford, CA, 94305-5427, USA.
    Background: Approximately 70% of all breast cancers express the estrogen receptor, and are regulated by estrogen. While the ovaries are the primary source of estrogen in premenopausal women, most breast cancer is diagnosed following menopause, when systemic levels of this hormone decline. Estrogen production from androgen precursors is catalyzed by the aromatase enzyme. Read More

    Prognostic value of PAM50 and risk of recurrence score in patients with early-stage breast cancer with long-term follow-up.
    Breast Cancer Res 2017 Nov 14;19(1):120. Epub 2017 Nov 14.
    Division of Cancer Medicine, Department of Oncology, Oslo University Hospital, Postbox 4953 Nydalen, 0424, Oslo, Norway.
    Background: The aim of this study was to investigate the prognostic value of the PAM50 intrinsic subtypes and risk of recurrence (ROR) score in patients with early breast cancer and long-term follow-up. A special focus was placed on hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) pN0 patients not treated with chemotherapy.

    Methods: Patients with early breast cancer (n = 653) enrolled in the observational Oslo1 study (1995-1998) were followed for distant recurrence and breast cancer death. Read More

    Reproductive profiles and risk of breast cancer subtypes: a multi-center case-only study.
    Breast Cancer Res 2017 Nov 7;19(1):119. Epub 2017 Nov 7.
    Department of Oncology, Leuven Multidisciplinary Breast Cancer, University Hospital Leuven, KU Leuven, Leuven, Belgium.
    Background: Previous studies have shown that reproductive factors are differentially associated with breast cancer (BC) risk by subtypes. The aim of this study was to investigate associations between reproductive factors and BC subtypes, and whether these vary by age at diagnosis.

    Methods: We used pooled data on tumor markers (estrogen and progesterone receptor, human epidermal growth factor receptor-2 (HER2)) and reproductive risk factors (parity, age at first full-time pregnancy (FFTP) and age at menarche) from 28,095 patients with invasive BC from 34 studies participating in the Breast Cancer Association Consortium (BCAC). Read More

    Addition of T2-guided optical tomography improves noncontrast breast magnetic resonance imaging diagnosis.
    Breast Cancer Res 2017 Oct 24;19(1):117. Epub 2017 Oct 24.
    Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH, 03755, USA.
    Background: While dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) is recognized as the most sensitive examination for breast cancer detection, it has a substantial false positive rate and gadolinium (Gd) contrast agents are not universally well tolerated. As a result, alternatives to diagnosing breast cancer based on endogenous contrast are of growing interest. In this study, endogenous near-infrared spectral tomography (NIRST) guided by T2 MRI was evaluated to explore whether the combined imaging modality, which does not require contrast injection or involve ionizing radiation, can achieve acceptable diagnostic performance. Read More

    Roles of BCCIP deficiency in mammary tumorigenesis.
    Breast Cancer Res 2017 Oct 18;19(1):115. Epub 2017 Oct 18.
    Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, USA.
    Background: Dysregulated DNA repair and cell proliferation controls are essential driving forces in mammary tumorigenesis. BCCIP was originally identified as a BRCA2 and CDKN1A interacting protein that has been implicated in maintenance of genomic stability, cell cycle regulation, and microtubule dynamics. The aims of this study were to determine whether BCCIP deficiency contributes to mammary tumorigenesis, especially for a subset of breast cancers with 53BP1 abnormality, and to reveal the mechanistic implications of BCCIP in breast cancer interventions. Read More

    A novel and fully automated mammographic texture analysis for risk prediction: results from two case-control studies.
    Breast Cancer Res 2017 Oct 18;19(1):114. Epub 2017 Oct 18.
    Centre for Imaging Science, School of Health Sciences, University of Manchester, Stopford Building, Oxford Road, Manchester, M13 9PT, UK.
    Background: The percentage of mammographic dense tissue (PD) is an important risk factor for breast cancer, and there is some evidence that texture features may further improve predictive ability. However, relatively little work has assessed or validated textural feature algorithms using raw full field digital mammograms (FFDM).

    Method: A case-control study nested within a screening cohort (age 46-73 years) from Manchester UK was used to develop a texture feature risk score (264 cases diagnosed at the same time as mammogram of the contralateral breast, 787 controls) using the least absolute shrinkage and selection operator (LASSO) method for 112 features, and validated in a second case-control study from the same cohort but with cases diagnosed after the index mammogram (317 cases, 931 controls). Read More

    Gene expression modules in primary breast cancers as risk factors for organotropic patterns of first metastatic spread: a case control study.
    Breast Cancer Res 2017 Oct 13;19(1):113. Epub 2017 Oct 13.
    School of Cancer Studies, CRUK King's Health Partners Centre, King's College London, Guy's Campus, London, SE1 1UL, UK.
    Background: Metastases from primary breast cancers can involve single or multiple organs at metastatic disease diagnosis. Molecular risk factors for particular patterns of metastastic spread in a clinical population are limited.

    Methods: A case-control design including 1357 primary breast cancers was used to study three distinct clinical patterns of metastasis, which occur within the first six months of metastatic disease: bone and visceral metasynchronous spread, bone-only, and visceral-only metastasis. Read More

    Proteomic profiling of breast cancer metabolism identifies SHMT2 and ASCT2 as prognostic factors.
    Breast Cancer Res 2017 Oct 11;19(1):112. Epub 2017 Oct 11.
    Department of Gynaecology, Martin-Luther-University, Halle-Wittenberg, Ernst-Grube-Str. 40, 06120, Halle (Saale), Germany.
    Background: Breast cancer tumors are known to be highly heterogeneous and differences in their metabolic phenotypes, especially at protein level, are less well-understood. Profiling of metabolism-related proteins harbors the potential to establish new patient stratification regimes and biomarkers promoting individualized therapy. In our study, we aimed to examine the relationship between metabolism-associated protein expression profiles and clinicopathological characteristics in a large cohort of breast cancer patients. Read More

    FUT8 promotes breast cancer cell invasiveness by remodeling TGF-β receptor core fucosylation.
    Breast Cancer Res 2017 Oct 5;19(1):111. Epub 2017 Oct 5.
    Institute of Biomedical Sciences, Academia Sinica, Taipei, 11529, Taiwan.
    Background: Core fucosylation (addition of fucose in α-1,6-linkage to core N-acetylglucosamine of N-glycans) catalyzed by fucosyltransferase 8 (FUT8) is critical for signaling receptors involved in many physiological and pathological processes such as cell growth, adhesion, and tumor metastasis. Transforming growth factor-β (TGF-β)-induced epithelial-mesenchymal transition (EMT) regulates the invasion and metastasis of breast tumors. However, whether receptor core fucosylation affects TGF-β signaling during breast cancer progression remains largely unknown. Read More

    Endophilin A2 promotes HER2 internalization and sensitivity to trastuzumab-based therapy in HER2-positive breast cancers.
    Breast Cancer Res 2017 Oct 3;19(1):110. Epub 2017 Oct 3.
    Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
    Background: Human epidermal growth factor receptor-2 (HER2) is amplified and a clinical target in a subset of human breast cancers with high rates of metastasis. Targeted therapies involving the antibody trastuzumab and trastuzumab-emtansine (T-DM1) have greatly improved outcomes for HER2-positive (HER2+) breast cancer patients. However, resistance to these targeted therapies can develop and limit their efficacy. Read More

    Alcohol consumption and breast tumor gene expression.
    Breast Cancer Res 2017 Sep 12;19(1):108. Epub 2017 Sep 12.
    Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts Amherst, 715 N Pleasant Street, Amherst, MA, 01003, USA.
    Background: Alcohol consumption is an established risk factor for breast cancer and the association generally appears stronger among estrogen receptor (ER)-positive tumors. However, the biological mechanisms underlying this association are not completely understood.

    Methods: We analyzed messenger RNA (mRNA) microarray data from both invasive breast tumors (N = 602) and tumor-adjacent normal tissues (N = 508) from participants diagnosed with breast cancer in the Nurses' Health Study (NHS) and NHSII. Read More

    Heterogeneous drug penetrance of veliparib and carboplatin measured in triple negative breast tumors.
    Breast Cancer Res 2017 Sep 11;19(1):107. Epub 2017 Sep 11.
    Department of Laboratory Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA.
    Background: Poly(ADP-ribose) polymerase inhibitors (PARPi), coupled to a DNA damaging agent is a promising approach to treating triple negative breast cancer (TNBC). However, not all patients respond; we hypothesize that non-response in some patients may be due to insufficient drug penetration. As a first step to testing this hypothesis, we quantified and visualized veliparib and carboplatin penetration in mouse xenograft TNBCs and patient blood samples. Read More

    Contrast-enhanced spectral mammography in neoadjuvant chemotherapy monitoring: a comparison with breast magnetic resonance imaging.
    Breast Cancer Res 2017 Sep 11;19(1):106. Epub 2017 Sep 11.
    Radiology Unit, Department of Diagnostic Imaging and Laboratory Medicine, Arcispedale Santa Maria Nuova - IRCCS, Viale Umberto I, No. 50, 42123, Reggio Emilia, Italy.
    Background: Neoadjuvant-chemotherapy (NAC) is considered the standard treatment for locally advanced breast carcinomas. Accurate assessment of disease response is fundamental to increase the chances of successful breast-conserving surgery and to avoid local recurrence. The purpose of this study was to compare contrast-enhanced spectral mammography (CESM) and contrast-enhanced-MRI (MRI) in the evaluation of tumor response to NAC. Read More

    ErbB3 drives mammary epithelial survival and differentiation during pregnancy and lactation.
    Breast Cancer Res 2017 Sep 8;19(1):105. Epub 2017 Sep 8.
    Department of Cancer Biology, Vanderbilt University School of Medicine, 2220 Pierce Avenue, Rm 749 Preston Research Building, Nashville, TN, 37232, USA.
    Background: During pregnancy, as the mammary gland prepares for synthesis and delivery of milk to newborns, a luminal mammary epithelial cell (MEC) subpopulation proliferates rapidly in response to systemic hormonal cues that activate STAT5A. While the receptor tyrosine kinase ErbB4 is required for STAT5A activation in MECs during pregnancy, it is unclear how ErbB3, a heterodimeric partner of ErbB4 and activator of phosphatidyl inositol-3 kinase (PI3K) signaling, contributes to lactogenic expansion of the mammary gland.

    Methods: We assessed mRNA expression levels by expression microarray of mouse mammary glands harvested throughout pregnancy and lactation. Read More

    SPEN, a new player in primary cilia formation and cell migration in breast cancer.
    Breast Cancer Res 2017 Sep 6;19(1):104. Epub 2017 Sep 6.
    Division of Experimental Medicine, Department of Oncology and Surgery, McGill University, Montréal, PQ, H3A 0G4, Canada.
    Background: The primary cilium is a microtubule-based and nonmotile organelle functioning as a cellular antenna that is involved in the regulation of cell proliferation, differentiation, and migration. In breast cancer cells, the primary cilium is a structure that decreases in incidence with increasing degrees of transformation and may be biologically more important in estrogen receptor (ERα)-negative breast cancer cells. Split ends (SPEN) is an ERα corepressor that we have identified as a tumor suppressor protein in ERα-positive breast cancer cells whose hormone-independent roles in breast cancer have never been explored. Read More

    Breast Tissue Organisation and its Association with Breast Cancer Risk.
    Breast Cancer Res 2017 Sep 6;19(1):103. Epub 2017 Sep 6.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Background: Mammographic percentage density is an established and important risk factor for breast cancer. In this paper, we investigate the role of the spatial organisation of (dense vs. fatty) regions of the breast defined from mammographic images in terms of breast cancer risk. Read More

    Pathobiology of the 129:Stat1 -/- mouse model of human age-related ER-positive breast cancer with an immune infiltrate-excluded phenotype.
    Breast Cancer Res 2017 Sep 2;19(1):102. Epub 2017 Sep 2.
    Center for Comparative Medicine, University of California at Davis, Davis, CA, USA.
    Background: Stat1 gene-targeted knockout mice (129S6/SvEvTac-Stat1 tm1Rds) develop estrogen receptor-positive (ER+), luminal-type mammary carcinomas at an advanced age. There is evidence for both host environment as well as tumor cell-intrinsic mechanisms to initiate tumorigenesis in this model. In this report, we summarize details of the systemic and mammary pathology at preneoplastic and tumor-bearing time points. Read More

    The BRCA1ness signature is associated significantly with response to PARP inhibitor treatment versus control in the I-SPY 2 randomized neoadjuvant setting.
    Breast Cancer Res 2017 Aug 25;19(1):99. Epub 2017 Aug 25.
    Agendia NV, Amsterdam, The Netherlands.
    Background: Patients with BRCA1-like tumors correlate with improved response to DNA double-strand break-inducing therapy. A gene expression-based classifier was developed to distinguish between BRCA1-like and non-BRCA1-like tumors. We hypothesized that these tumors may also be more sensitive to PARP inhibitors than standard treatments. Read More

    Association of pre-chemotherapy peripheral blood pro-inflammatory and coagulation factors with reduced relative dose intensity in women with breast cancer.
    Breast Cancer Res 2017 Aug 29;19(1):101. Epub 2017 Aug 29.
    City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, CA, USA.
    Background: Chemotherapy decreases the risk of relapse and mortality in early-stage breast cancer (BC), but it comes with the risk of toxicity. Chemotherapy efficacy depends on relative dose intensity (RDI), and an RDI < 85% is associated with worse overall survival. The pro-inflammatory (interleukin (IL)-6, C-reactive protein (CRP)) and coagulation factors (D-dimer) serve as biomarkers of aging. Read More

    Tissue-based associations of mammographic breast density with breast stem cell markers.
    Breast Cancer Res 2017 Aug 29;19(1):100. Epub 2017 Aug 29.
    Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, MN, 55905, USA.
    Background: Mammographic breast density is a well-established, strong breast cancer risk factor but the biology underlying this association remains unclear. Breast density may reflect underlying alterations in the size and activity of the breast stem cell pool. We examined, for the first time, associations of CD44, CD24, and aldehyde dehydrogenase family 1 member A1 (ALDH1A1) breast stem cell markers with breast density. Read More

    Assessment of the prognostic role of a 94-single nucleotide polymorphisms risk score in early breast cancer in the SIGNAL/PHARE prospective cohort: no correlation with clinico-pathological characteristics and outcomes.
    Breast Cancer Res 2017 Aug 22;19(1):98. Epub 2017 Aug 22.
    Centre de Recherche en Cancérologie de Lyon, INSERM U1052 - Centre Léon Bérard, 28 rue Laennec, 69373, Lyon, France.
    Background: Genome-wide association studies (GWAS) have to date identified 94 genetic variants (single nucleotide polymorphisms (SNPs)) associated with risk of developing breast cancer. A score based on the combined effect of the 94 risk alleles can be calculated to measure the global risk of breast cancer. We aimed to test the hypothesis that the 94-SNP-based risk score is associated with clinico-pathological characteristics, breast cancer subtypes and outcomes in early breast cancer. Read More

    The ninth ENBDC Weggis meeting: growth and in-depth characterisation of normal and neoplastic breast cells.
    Breast Cancer Res 2017 Aug 22;19(1):96. Epub 2017 Aug 22.
    INSERM U1218, Institut Bergonie, University of Bordeaux, 229 cours de l'Argonne, 33076, Bordeaux, France.
    Mammary gland biologists gathered for the ninth annual workshop of the European Network for Breast Development and Cancer (ENBDC) at Weggis on the shores of Lake Lucerne in March 2017. The main themes were oestrogen receptor alpha signalling, new techniques for mammary cell culture, CRISPR screening and proteogenomics. Read More

    Combining quantitative and qualitative breast density measures to assess breast cancer risk.
    Breast Cancer Res 2017 Aug 22;19(1):97. Epub 2017 Aug 22.
    Department of Radiology, University of California, San Francisco, CA, USA.
    Background: Accurately identifying women with dense breasts (Breast Imaging Reporting and Data System [BI-RADS] heterogeneously or extremely dense) who are at high breast cancer risk will facilitate discussions of supplemental imaging and primary prevention. We examined the independent contribution of dense breast volume and BI-RADS breast density to predict invasive breast cancer and whether dense breast volume combined with Breast Cancer Surveillance Consortium (BCSC) risk model factors (age, race/ethnicity, family history of breast cancer, history of breast biopsy, and BI-RADS breast density) improves identifying women with dense breasts at high breast cancer risk.

    Methods: We conducted a case-control study of 1720 women with invasive cancer and 3686 control subjects. Read More

    White blood cell DNA methylation and risk of breast cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO).
    Breast Cancer Res 2017 Aug 18;19(1):94. Epub 2017 Aug 18.
    Department of Civil and Environmental Engineering, University of Massachusetts, Amherst, MA, 01003, USA.
    Background: Several studies have suggested that global DNA methylation in circulating white blood cells (WBC) is associated with breast cancer risk.

    Methods: To address conflicting results and concerns that the findings for WBC DNA methylation in some prior studies may reflect disease effects, we evaluated the relationship between global levels of WBC DNA methylation in white blood cells and breast cancer risk in a case-control study nested within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) cohort. A total of 428 invasive breast cancer cases and 419 controls, frequency matched on age at entry (55-59, 60-64, 65-69, ≥70 years), year of entry (on/before September 30, 1997, on/after October 1, 1997) and period of DNA extraction (previously extracted, newly extracted) were included. Read More

    Calmodulin-like protein 3 is an estrogen receptor alpha coregulator for gene expression and drug response in a SNP, estrogen, and SERM-dependent fashion.
    Breast Cancer Res 2017 Aug 18;19(1):95. Epub 2017 Aug 18.
    Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
    Background: We previously performed a case-control genome-wide association study in women treated with selective estrogen receptor modulators (SERMs) for breast cancer prevention and identified single nucleotide polymorphisms (SNPs) in ZNF423 as potential biomarkers for response to SERM therapy. The ZNF423rs9940645 SNP, which is approximately 200 bp away from the estrogen response elements, resulted in the SNP, estrogen, and SERM-dependent regulation of ZNF423 expression and, "downstream", that of BRCA1.

    Methods: Electrophoretic mobility shift assay-mass spectrometry was performed to identify proteins binding to the ZNF423 SNP and coordinating with estrogen receptor alpha (ERα). Read More

    Selinexor (KPT-330) demonstrates anti-tumor efficacy in preclinical models of triple-negative breast cancer.
    Breast Cancer Res 2017 Aug 15;19(1):93. Epub 2017 Aug 15.
    Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA.
    Background: Selinexor (KPT-330) is an oral agent that has been shown to inhibit the nuclear exporter XPO1. Given the pressing need for novel therapies for triple-negative breast cancer (TNBC), we sought to determine the antitumor effects of selinexor in vitro and in vivo.

    Methods: Twenty-six breast cancer cell lines of different breast cancer subtypes were treated with selinexor in vitro. Read More

    Concurrent antitumor and bone-protective effects of everolimus in osteotropic breast cancer.
    Breast Cancer Res 2017 Aug 9;19(1):92. Epub 2017 Aug 9.
    Division of Endocrinology, Diabetes and Bone Diseases, Department of Medicine III, Technical University Dresden, Fetscherstraße 74, D-01307, Dresden, Germany.
    Background: The mammalian target of rapamycin inhibitor everolimus is approved as an antitumor agent in advanced estrogen receptor-positive breast cancer. Surrogate bone marker data from clinical trials suggest effects on bone metabolism, but the mode of action of everolimus in bone biology remains unclear. In this study, we assessed potential bone-protective effects of everolimus in the context of osteotropic tumors. Read More

    Effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes and PD-L1 expression in breast cancer and its clinical significance.
    Breast Cancer Res 2017 Aug 7;19(1):91. Epub 2017 Aug 7.
    Department of Pathology, Yale University School of Medicine, 310 Cedar St, PO Box 208023, New Haven, CT, 06520-8023, USA.
    Background: The effects of neoadjuvant chemotherapy on immune markers remain largely unknown. The specific aim of this study was to assess stromal tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) protein expression in a cohort of breast cancer patients treated with neoadjuvant chemotherapy.

    Methods: Using quantitative immunofluorescence, we investigated stromal TILs and PD-L1 protein expression in pre-treatment and residual breast cancer tissue from a Yale Cancer Center patient cohort of 58 patients diagnosed with breast cancer from 2003 to 2009 and treated with neoadjuvant chemotherapy. Read More

    Inhibition of basal-like breast cancer growth by FTY720 in combination with epidermal growth factor receptor kinase blockade.
    Breast Cancer Res 2017 Aug 4;19(1):90. Epub 2017 Aug 4.
    Kolling Institute, University of Sydney, Royal North Shore Hospital, St Leonards, NSW, 2065, Australia.
    Background: New molecular targets are needed for women with triple-negative breast cancer (TNBC). This pre-clinical study investigated the combination of the EGFR inhibitor gefitinib with the sphingosine kinase (SphK) inhibitor FTY720 (Fingolimod), aiming to block tumorigenic signaling downstream of IGFBP-3, which is abundantly expressed in basal-like TNBC.

    Methods: In studies of breast cancer cell growth in culture, proliferation was monitored by IncuCyte live-cell imaging, and protein abundance was determined by western blotting. Read More

    AKT1low quiescent cancer cells persist after neoadjuvant chemotherapy in triple negative breast cancer.
    Breast Cancer Res 2017 Aug 1;19(1):88. Epub 2017 Aug 1.
    Massachusetts General Hospital Cancer Center, Richard B. Simches Research Building, 185 Cambridge Street, Boston, MA, 02114, USA.
    Background: Absence of pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) correlates with poor long-term survival in patients with triple negative breast cancer (TNBC). These incomplete treatment responses are likely determined by mechanisms that enable cancer cells to resist being killed. However, the detailed characterization of a drug-resistant cancer cell state in residual TNBC tissue after NACT has remained elusive. Read More

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