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Breast Cancer Research: BCR

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https://www.readbyqxmd.com/read/28899409/alcohol-consumption-and-breast-tumor-gene-expression
#1
Jun Wang, Yujing J Heng, A Heather Eliassen, Rulla M Tamimi, Aditi Hazra, Vincent J Carey, Christine B Ambrosone, Victor P de Andrade, Adam Brufsky, Fergus J Couch, Tari A King, Francesmary Modugno, Celine M Vachon, David J Hunter, Andrew H Beck, Susan E Hankinson
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...
September 12, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28893315/heterogeneous-drug-penetrance-of-veliparib-and-carboplatin-measured-in-triple-negative-breast-tumors
#2
Imke H Bartelink, Brendan Prideaux, Gregor Krings, Lisa Wilmes, Pei Rong Evelyn Lee, Pan Bo, Byron Hann, Jean-Philippe Coppé, Diane Heditsian, Lamorna Swigart-Brown, Ella F Jones, Sergey Magnitsky, Ron J Keizer, Niels de Vries, Hilde Rosing, Nela Pawlowska, Scott Thomas, Mallika Dhawan, Rahul Aggarwal, Pamela N Munster, Laura J Esserman, Weiming Ruan, Alan H B Wu, Douglas Yee, Véronique Dartois, Radojka M Savic, Denise M Wolf, Laura van 't Veer
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. METHODS: MDA-MB-231, HCC70 or MDA-MB-436 human TNBC cells were implanted in 41 beige SCID mice...
September 11, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28893303/contrast-enhanced-spectral-mammography-in-neoadjuvant-chemotherapy-monitoring-a-comparison-with-breast-magnetic-resonance-imaging
#3
Valentina Iotti, Sara Ravaioli, Rita Vacondio, Chiara Coriani, Sabrina Caffarri, Roberto Sghedoni, Andrea Nitrosi, Moira Ragazzi, Elisa Gasparini, Cristina Masini, Giancarlo Bisagni, Giuseppe Falco, Guglielmo Ferrari, Luca Braglia, Alberto Del Prato, Ivana Malavolti, Vladimiro Ginocchi, Pierpaolo Pattacini
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. METHODS: This prospective study was approved by the institutional review board and written informed consent was obtained...
September 11, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28886748/erbb3-drives-mammary-epithelial-survival-and-differentiation-during-pregnancy-and-lactation
#4
Michelle M Williams, David B Vaught, Meghan Morrison Joly, Donna J Hicks, Violeta Sanchez, Philip Owens, Bushra Rahman, David L Elion, Justin M Balko, Rebecca S Cook
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...
September 8, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28877752/spen-a-new-player-in-primary-cilia-formation-and-cell-migration-in-breast-cancer
#5
Stéphanie Légaré, Catherine Chabot, Mark Basik
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...
September 6, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28877713/breast-tissue-organisation-and-its-association-with-breast-cancer-risk
#6
Maya Alsheh Ali, Kamila Czene, Louise Eriksson, Per Hall, Keith Humphreys
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. METHODS: We present a novel approach that provides a thorough description of the spatial organisation of different types of tissue in the breast. Each mammogram is first segmented into four regions (fatty, semi-fatty, semi-dense and dense tissue)...
September 6, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28865492/pathobiology-of-the-129-stat1-mouse-model-of-human-age-related-er-positive-breast-cancer-with-an-immune-infiltrate-excluded-phenotype
#7
Hidetoshi Mori, Jane Q Chen, Robert D Cardiff, Zsófia Pénzváltó, Neil E Hubbard, Louis Schuetter, Russell C Hovey, Josephine F Trott, Alexander D Borowsky
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. In addition, we investigate tumor progression in the 129:Stat1 (-/-) host compared with wild-type 129/SvEv, and we describe the immune cell reaction to the tumors...
September 2, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28851415/association-of-pre-chemotherapy-peripheral-blood-pro-inflammatory-and-coagulation-factors-with-reduced-relative-dose-intensity-in-women-with-breast-cancer
#8
Yuan Yuan, Nilesh Vora, Can-Lan Sun, Daneng Li, Enrique Soto-Perez-de-Celis, Joanne Mortimer, The-Hang Luu, George Somlo, James Waisman, David Smith, Joseph Chao, Vani Katheria, Timothy Synold, Vivi Tran, Shu Mi, Abrahm Levi, Anait Arsenyan, Jennifer Choi, Laura Zavala, Susan Yost, Arti Hurria
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. The purpose of this study is to determine if these biomarkers are associated with reduced RDI in women with stage I-III BC...
August 29, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28851411/tissue-based-associations-of-mammographic-breast-density-with-breast-stem-cell-markers
#9
Lusine Yaghjyan, Ethan Stoll, Karthik Ghosh, Christopher G Scott, Matthew R Jensen, Kathleen R Brandt, Daniel Visscher, Celine M Vachon
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. METHODS: We included in this study 64 asymptomatic healthy women who previously volunteered for a unique biopsy study of normal breast tissue at the Mayo Clinic (2006-2008)...
August 29, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28851423/the-brca1ness-signature-is-associated-significantly-with-response-to-parp-inhibitor-treatment-versus-control-in-the-i-spy-2-randomized-neoadjuvant-setting
#10
Tesa M Severson, Denise M Wolf, Christina Yau, Justine Peeters, Diederik Wehkam, Philip C Schouten, Suet-Feung Chin, Ian J Majewski, Magali Michaut, Astrid Bosma, Bernard Pereira, Tycho Bismeijer, Lodewyk Wessels, Carlos Caldas, René Bernards, Iris M Simon, Annuska M Glas, Sabine Linn, Laura van 't Veer
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. METHODS: A diagnostic gene expression signature (BRCA1ness) was developed using a centroid model with 128 triple-negative breast cancer samples from the EU FP7 RATHER project...
August 25, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28830573/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
#11
Elsa Curtit, Xavier Pivot, Julie Henriques, Sophie Paget-Bailly, Pierre Fumoleau, Maria Rios, Hervé Bonnefoi, Thomas Bachelot, Patrick Soulié, Christelle Jouannaud, Hugues Bourgeois, Thierry Petit, Isabelle Tennevet, David Assouline, Marie-Christine Mathieu, Jean-Philippe Jacquin, Sandrine Lavau-Denes, Ariane Darut-Jouve, Jean-Marc Ferrero, Carole Tarpin, Christelle Lévy, Valérie Delecroix, Véronique Trillet-Lenoir, Oana Cojocarasu, Jérôme Meunier, Jean-Yves Pierga, Pierre Kerbrat, Céline Faure-Mercier, Hélène Blanché, Mourad Sahbatou, Anne Boland, Delphine Bacq, Céline Besse, Gilles Thomas, Jean-François Deleuze, Iris Pauporté, Gilles Romieu, David G Cox
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...
August 22, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28830566/the-ninth-enbdc-weggis-meeting-growth-and-in-depth-characterisation-of-normal-and-neoplastic-breast-cells
#12
Katrin E Wiese, Romain J Amante, Maria dM Vivanco, Mohamed Bentires-Alj, Richard D Iggo
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.
August 22, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28830497/combining-quantitative-and-qualitative-breast-density-measures-to-assess-breast-cancer-risk
#13
Karla Kerlikowske, Lin Ma, Christopher G Scott, Amir P Mahmoudzadeh, Matthew R Jensen, Brian L Sprague, Louise M Henderson, V Shane Pankratz, Steven R Cummings, Diana L Miglioretti, Celine M Vachon, John A Shepherd
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...
August 22, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28821281/white-blood-cell-dna-methylation-and-risk-of-breast-cancer-in-the-prostate-lung-colorectal-and-ovarian-cancer-screening-trial-plco
#14
Susan R Sturgeon, J Richard Pilsner, Kathleen F Arcaro, Kaoru Ikuma, Haotian Wu, Soon-Mi Kim, Nayha Chopra-Tandon, Adam R Karpf, Regina G Ziegler, Catherine Schairer, Raji Balasubramanian, David A Reckhow
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...
August 18, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28821270/calmodulin-like-protein-3-is-an-estrogen-receptor-alpha-coregulator-for-gene-expression-and-drug-response-in-a-snp-estrogen-and-serm-dependent-fashion
#15
Sisi Qin, James N Ingle, Mohan Liu, Jia Yu, D Lawrence Wickerham, Michiaki Kubo, Richard M Weinshilboum, Liewei Wang
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...
August 18, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28810913/selinexor-kpt-330-demonstrates-anti-tumor-efficacy-in-preclinical-models-of-triple-negative-breast-cancer
#16
Natalia Paez Arango, Erkan Yuca, Ming Zhao, Kurt W Evans, Stephen Scott, Charissa Kim, Ana Maria Gonzalez-Angulo, Filip Janku, Naoto T Ueno, Debu Tripathy, Argun Akcakanat, Aung Naing, Funda Meric-Bernstam
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. Cell proliferation assays were used to measure the half-maximal inhibitory concentration (IC50) and to test the effects in combination with chemotherapy...
August 15, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28793923/concurrent-antitumor-and-bone-protective-effects-of-everolimus-in-osteotropic-breast-cancer
#17
Andrew J Browne, Marie L Kubasch, Andy Göbel, Peyman Hadji, David Chen, Martina Rauner, Friedrich Stölzel, Lorenz C Hofbauer, Tilman D Rachner
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. METHODS: The effects of everolimus on cancer cell viability in vitro and on tumor growth in vivo were assessed...
August 9, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28784153/effect-of-neoadjuvant-chemotherapy-on-tumor-infiltrating-lymphocytes-and-pd-l1-expression-in-breast-cancer-and-its-clinical-significance
#18
Vasiliki Pelekanou, Daniel E Carvajal-Hausdorf, Mehmet Altan, Brad Wasserman, Cristobal Carvajal-Hausdorf, Hallie Wimberly, Jason Brown, Donald Lannin, Lajos Pusztai, David L Rimm
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...
August 7, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28778177/inhibition-of-basal-like-breast-cancer-growth-by-fty720-in-combination-with-epidermal-growth-factor-receptor-kinase-blockade
#19
Janet L Martin, Sohel M Julovi, Mike Z Lin, Hasanthi C de Silva, Frances M Boyle, Robert C Baxter
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...
August 4, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28764748/a-phase-i-trial-of-ganetespib-in-combination-with-paclitaxel-and-trastuzumab-in-patients-with-human-epidermal-growth-factor-receptor-2-her2-positive-metastatic-breast-cancer
#20
Komal Jhaveri, Rui Wang, Eleonora Teplinsky, Sarat Chandarlapaty, David Solit, Karen Cadoo, James Speyer, Gabriella D'Andrea, Sylvia Adams, Sujata Patil, Sofia Haque, Tara O'Neill, Kent Friedman, Francisco J Esteva, Clifford Hudis, Shanu Modi
BACKGROUND: Targeted therapies in HER2-positive metastatic breast cancer significantly improve outcomes but efficacy is limited by therapeutic resistance. HER2 is an acutely sensitive Heat Shock Protein 90 (HSP90) client and HSP90 inhibition can overcome trastuzumab resistance. Preclinical data suggest that HSP90 inhibition is synergistic with taxanes with the potential for significant clinical activity. We therefore tested ganetespib, a HSP90 inhibitor, in combination with paclitaxel and trastuzumab in patients with trastuzumab-refractory HER2-positive metastatic breast cancer...
August 2, 2017: Breast Cancer Research: BCR
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