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https://www.readbyqxmd.com/read/29753961/the-role-of-parp-inhibition-in-triple-negative-breast-cancer-unraveling-the-wide-spectrum-of-synthetic-lethality
#1
REVIEW
Marios Papadimitriou, Giannis Mountzios, Christos A Papadimitriou
Triple-negative breast cancer (TNBC) accounts for approximately 15-20% of all breast cancers and is characterized by a lack of immunohistochemical expression of estrogen receptors (ER), progesterone receptors (PR) and HER2. TNBC is associated with poor long-term outcomes compared with other breast cancer subtypes. Many of these tumors are also basal-like cancers which are characterized by an aggressive biological behavior with a distant recurrence peak observed early at 3 years following diagnosis. Furthermore, metastatic TNBC bears a dismal prognosis with an average survival of 12 months...
May 2, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29726012/rad50-germline-mutations-are-associated-with-poor-survival-in-brca1-2-negative-breast-cancer-patients
#2
Cong Fan, Juan Zhang, Tao Ouyang, Jinfeng Li, Tianfeng Wang, Zhaoqing Fan, Tie Fan, Benyao Lin, Yuntao Xie
RAD50 is a highly conserved DNA double-strand break (DSB) repair gene. However, the associations between RAD50 germline mutations and the survival and risk of breast cancer have not been fully elucidated. Here, we aimed to investigate the clinical impact of RAD50 germline mutations in a large cohort of unselected breast cancer patients. In this study, RAD50 germline mutations were determined using next-generation sequencing in 7657 consecutive unselected breast cancer patients without BRCA1/2 mutations. We also screened for RAD50 recurrent mutations (L719fs, K994fs, and H1269fs) in 5000 healthy controls using Sanger sequencing...
May 4, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29721177/a-pilot-study-of-durvalumab-and-tremelimumab-and-immunogenomic-dynamics-in-metastatic-breast-cancer
#3
Cesar August Santa-Maria, Taigo Kato, Jae-Hyun Park, Kazuma Kiyotani, Alfred Rademaker, Ami N Shah, Leeaht Gross, Luis Z Blanco, Sarika Jain, Lisa Flaum, Claudia Tellez, Regina Stein, Regina Uthe, William J Gradishar, Massimo Cristofanilli, Yusuke Nakamura, Francis J Giles
Immune checkpoint inhibitors produce modest responses in metastatic breast cancer, however, combination approaches may improve responses. A single arm pilot study was designed to determine the overall response rate (ORR) of durvalumab and tremelimumab, and evaluate immunogenomic dynamics in metastatic endocrine receptor (ER) positive or triple negative breast cancer (TNBC). Simon two-stage design indicated at least four responses from the first 18 patients were needed to proceed with the second stage. T-cell receptor (TCR) sequencing and immune-gene expression profiling were conducted at baseline and two months, whole exome sequencing was conducted at baseline...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29713086/carboplatin-in-brca1-2-mutated-and-triple-negative-breast-cancer-brcaness-subgroups-the-tnt-trial
#4
Andrew Tutt, Holly Tovey, Maggie Chon U Cheang, Sarah Kernaghan, Lucy Kilburn, Patrycja Gazinska, Julie Owen, Jacinta Abraham, Sophie Barrett, Peter Barrett-Lee, Robert Brown, Stephen Chan, Mitchell Dowsett, James M Flanagan, Lisa Fox, Anita Grigoriadis, Alexander Gutin, Catherine Harper-Wynne, Matthew Q Hatton, Katherine A Hoadley, Jyoti Parikh, Peter Parker, Charles M Perou, Rebecca Roylance, Vandna Shah, Adam Shaw, Ian E Smith, Kirsten M Timms, Andrew M Wardley, Gregory Wilson, Cheryl Gillett, Jerry S Lanchbury, Alan Ashworth, Nazneen Rahman, Mark Harries, Paul Ellis, Sarah E Pinder, Judith M Bliss
Germline mutations in BRCA1/2 predispose individuals to breast cancer (termed germline-mutated BRCA1/2 breast cancer, gBRCA-BC) by impairing homologous recombination (HR) and causing genomic instability. HR also repairs DNA lesions caused by platinum agents and PARP inhibitors. Triple-negative breast cancers (TNBCs) harbor subpopulations with BRCA1/2 mutations, hypothesized to be especially platinum-sensitive. Cancers in putative 'BRCAness' subgroups-tumors with BRCA1 methylation; low levels of BRCA1 mRNA (BRCA1 mRNA-low); or mutational signatures for HR deficiency and those with basal phenotypes-may also be sensitive to platinum...
April 30, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29622727/current-detection-rates-and-time-to-detection-of-all-identifiable-brca-carriers-in-the-greater-london-population
#5
Ranjit Manchanda, Oleg Blyuss, Faiza Gaba, Vladimir Sergeevich Gordeev, Chris Jacobs, Matthew Burnell, Carmen Gan, Rohan Taylor, Clare Turnbull, Rosa Legood, Alexey Zaikin, Antonis C Antoniou, Usha Menon, Ian Jacobs
BACKGROUND: BRCA carrier identification offers opportunities for early diagnoses, targeted treatment and cancer prevention. We evaluate BRCA- carrier detection rates in general and Ashkenazi Jewish (AJ) populations across Greater London and estimate time-to-detection of all identifiable BRCA carriers. METHODS: BRCA carrier data from 1993 to 2014 were obtained from National Health Service genetic laboratories and compared with modelled predictions of BRCA prevalence from published literature and geographical data from UK Office for National Statistics...
April 5, 2018: Journal of Medical Genetics
https://www.readbyqxmd.com/read/29575819/pik3ca-mutations-and-their-response-to-neoadjuvant-treatment-in-early-breast-cancer-a-systematic-review-and-meta-analysis
#6
Hongwei Fan, Chao Li, Qian Xiang, Ling Xu, Zhuo Zhang, Qianxin Liu, Tonttong Zhang, Ying Zhou, Xia Zhao, Yimin Cui
BACKGROUND: PIK3CA mutations frequently occur in breast cancer patients. This study was conducted to evaluate the relationship between PIK3CA mutations and neoadjuvant treatment response and to analyze the clinical implications. METHODS: PubMed, Embase, and the Cochrane database were searched for relevant studies in September 2017. The pooled risk ratio (RR) was estimated using fixed effects or random effects models according to heterogeneity among studies. RESULTS: This meta-analysis included 20 studies with 4392 patients...
March 25, 2018: Thoracic Cancer
https://www.readbyqxmd.com/read/29573125/risk-of-dipeptidyl-peptidase-4-dpp-4-inhibitors-on-site-specific-cancer-a-systematic-review-and-meta-analysis
#7
REVIEW
Jetty A Overbeek, Marina Bakker, Amber A W A van der Heijden, Myrthe P P van Herk-Sukel, Ron M C Herings, Giel Nijpels
BACKGROUND: The long-term impact of DPP-4 inhibition is unknown and there are concerns about the influence of DPP-4 inhibition on carcinogenesis of the pancreas and thyroid. As DPP-4 is a rather unselective enzyme present in many tissues, we focused on all specific cancer types. METHODS: PubMed and EMBASE were searched between Jan 2005 and Apr 2017 to identify studies comparing DPP-4 inhibitors with either placebo or active drugs on cancer risk. Studies were included if they reported on at least one specific cancer outcome and had a follow-up of at least one year after start of drug use...
March 23, 2018: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/29528717/malignant-mesothelioma-in-individuals-with-nonmesothelial-neoplasms
#8
Kelly J Butnor, Elizabeth N Pavlisko, Thomas A Sporn, Victor L Roggli
CONTEXT: - Malignant mesothelioma (MM) is a component of the BAP1 tumor predisposition syndrome. Other than in BAP1 familial studies, nonmesothelial neoplasms in individuals with MM has not been comprehensively assessed. OBJECTIVE: - To assess the spectrum and prevalence of nonmesothelial neoplasms in individuals with MM. DESIGN: - Individuals with MM and second neoplasms were identified from a database of 3900 MM cases. The expected prevalence of each type of neoplasm was calculated and compared with the actual prevalence in the study population using available Surveillance, Epidemiology, and End Results data and other published data...
March 12, 2018: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29492181/frequency-of-brca1-and-brca2-causative-founder-variants-in-ovarian-cancer-patients-in-south-east-poland
#9
Tomasz Kluz, Andrzej Jasiewicz, Elżbieta Marczyk, Robert Jach, Anna Jakubowska, Jan Lubiński, Steven A Narod, Jacek Gronwald
Background: Causative variants in BRCA1 and BRCA2 are well-established risk factors for breast and ovarian cancer. In Poland, the causative founder variants in the BRCA1 are responsible for a significant proportion of ovarian cancer cases, however, regional differences in the frequencies of various mutations may exist. The spectrum and frequency of BRCA1/2 mutations between ovarian cancer patients have not yet been studied in the region of South-East Poland. Methods: We examined 158 consecutive unselected cases of ovarian cancer patients from the region of Podkarpacie...
2018: Hereditary Cancer in Clinical Practice
https://www.readbyqxmd.com/read/29482741/prospective-analysis-of-safety-and-efficacy-of-medical-cannabis-in-large-unselected-population-of-patients-with-cancer
#10
Lihi Bar-Lev Schleider, Raphael Mechoulam, Violeta Lederman, Mario Hilou, Ori Lencovsky, Oded Betzalel, Liat Shbiro, Victor Novack
BACKGROUND: Cancer is a major public health problem as the leading cause of death. Palliative treatment aimed to alleviate pain and nausea in patients with advanced disease is a cornerstone of oncology. In 2007, the Israeli Ministry of Health began providing approvals for medical cannabis for the palliation of cancer symptoms. The aim of this study is to characterize the epidemiology of cancer patients receiving medical cannabis treatment and describe the safety and efficacy of this therapy...
March 2018: European Journal of Internal Medicine
https://www.readbyqxmd.com/read/29465777/expression-of-mage-a-and-ny-eso-1-cancer-testis-antigens-is-enriched-in-triple-negative-invasive-breast-cancers
#11
Ashwini Raghavendra, Priyakshi Kalita-de Croft, Ana C Vargas, Chanel E Smart, Peter T Simpson, Jodi M Saunus, Sunil R Lakhani
AIMS: A better understanding of the expression of cancer/testis antigens (CTAs) in breast cancer might enable the identification of new immunotherapy options, especially for triple-negative (TN) tumours, which lack expression of the conventional therapeutic targets oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. The aim of this study was to quantify the expression of MAGE-A and NY-ESO-1 CTAs in breast cancer, and relate this to known clinicopathological parameters...
February 21, 2018: Histopathology
https://www.readbyqxmd.com/read/29405995/survey-of-gynecological-carcinosarcomas-in-families-with-breast-and-ovarian-cancer-predisposition
#12
Carla B Ripamonti, Siranoush Manoukian, Bernard Peissel, Jacopo Azzollini, Maria Luisa Carcangiu, Paolo Radice
Carcinosarcomas (CSs) are biphasic neoplasms composed of high grade, malignant, epithelial and mesenchymal elements. The incidence of gynecological CSs (GCSs) is 0.4/100,000 women per year. Patients affected with GCSs have been occasionally reported in Hereditary Breast Ovarian Cancer (HBOC) families, including a few cases with pathogenic variants in BRCA1/BRCA2 genes. The prevalence and the association of GCSs in HBOC families have not been systematically investigated. Thus, we searched for families with GCSs in the HBOC registry of the National Cancer Institute of Milan...
February 2018: Cancer Genetics
https://www.readbyqxmd.com/read/29361001/cost-effectiveness-of-population-based-brca1-brca2-rad51c-rad51d-brip1-palb2-mutation-testing-in-unselected-general-population-women
#13
Ranjit Manchanda, Shreeya Patel, Vladimir S Gordeev, Antonis C Antoniou, Shantel Smith, Andrew Lee, John L Hopper, Robert J MacInnis, Clare Turnbull, Susan J Ramus, Simon A Gayther, Paul D P Pharoah, Usha Menon, Ian Jacobs, Rosa Legood
Background: The cost-effectiveness of population-based panel testing for high- and moderate-penetrance ovarian cancer (OC)/breast cancer (BC) gene mutations is unknown. We evaluate the cost-effectiveness of population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 mutation testing compared with clinical criteria/family history (FH) testing in unselected general population women. Methods: A decision-analytic model comparing lifetime costs and effects of criteria/FH-based BRCA1/BRCA2 testing is compared with BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing in those fulfilling clinical criteria/strong FH of cancer (≥10% BRCA1/BRCA2 probability) and all women age 30 years or older...
January 18, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29335925/germline-deleterious-mutations-in-genes-other-than-brca2-are-infrequent-in-male-breast-cancer
#14
Florentia Fostira, Emmanouil Saloustros, Paraskevi Apostolou, Andromahi Vagena, Despoina Kalfakakou, Davide Mauri, Dimitrios Tryfonopoulos, Vassileios Georgoulias, Drakoulis Yannoukakos, Georgios Fountzilas, Irene Konstantopoulou
PURPOSE: Male breast cancer (MBC) is a rare cancer entity, with mutations in BRCA1 and BRCA2 genes accounting for ~ 10% of patients. Multiple-gene sequencing has already entered clinical practice for female breast cancer, whereas the performance of panel testing in MBC has not been studied extensively. Therefore, the aim of this study was to evaluate the clinical utility of panel testing for MBC, by the largest gene panel used so far, through investigation of patients deriving from a population with known founder effects...
May 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29331750/phosphoinositide-3-kinase-inhibitors-in-advanced-breast-cancer-a-systematic-review-and-meta-analysis
#15
REVIEW
Jacques Raphael, Danielle Desautels, Kathleen I Pritchard, Ekaterina Petkova, Prakeshkumar S Shah
Phosphoinositide 3-kinase (PI3K) inhibitors may overcome drug resistance and improve advanced breast cancer (ABC) outcomes. We conducted a systematic review and meta-analysis to assess the efficacy and safety of adding a PI3K inhibitor to the standard of care (SOC) treatment in ABC. The electronic databases Ovid, PubMed, Cochrane Central Register of Controlled Trials and Embase, were searched for relevant randomised trials. Pooled hazard ratios (HRs) for progression-free survival (PFS) and pooled risk ratios (RRs) for objective response rates (ORRs), disease control rates (DCRs) and toxicity were meta-analysed using the Mantel-Haenszel method and generic inverse variance...
March 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29315233/dissecting-time-from-tumor-related-gene-expression-variability-in-bilateral-breast-cancer
#16
Maurizio Callari, Matteo Dugo, Patrizia Miodini, Silvia Veneroni, Giampaolo Bianchini, Maria Grazia Daidone, Vera Cappelletti
Metachronous (MBC) and synchronous bilateral breast tumors (SBC) are mostly distinct primaries, whereas paired primaries and their local recurrences (LRC) share a common origin. Intra-pair gene expression variability in MBC, SBC, and LRC derives from time/tumor microenvironment-related and tumor genetic background-related factors and pairs represents an ideal model for trying to dissect tumor-related from microenvironment-related variability. Pairs of tumors derived from women with SBC ( n = 18), MBC ( n = 11), and LRC ( n = 10) undergoing local-regional treatment were profiled for gene expression; similarity between pairs was measured using an intraclass correlation coefficient (ICC) computed for each gene and compared using analysis of variance (ANOVA)...
January 9, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29242214/expressed-gene-fusions-as-frequent-drivers-of-poor-outcomes-in-hormone-receptor-positive-breast-cancer
#17
Karina J Matissek, Maristela L Onozato, Sheng Sun, Zongli Zheng, Andrew Schultz, Jesse Lee, Kristofer Patel, Piiha-Lotta Jerevall, Srinivas Vinod Saladi, Allison Macleay, Mehrad Tavallai, Tanja Badovinac-Crnjevic, Carlos Barrios, Nuran Beşe, Arlene Chan, Yanin Chavarri-Guerra, Marcio Debiasi, Elif Demirdögen, Ünal Egeli, Sahsuvar Gökgöz, Henry Gomez, Pedro Liedke, Ismet Tasdelen, Sahsine Tolunay, Gustavo Werutsky, Jessica St Louis, Nora Horick, Dianne M Finkelstein, Long Phi Le, Aditya Bardia, Paul E Goss, Dennis C Sgroi, A John Iafrate, Leif W Ellisen
We sought to uncover genetic drivers of hormone receptor-positive (HR+ ) breast cancer, using a targeted next-generation sequencing approach for detecting expressed gene rearrangements without prior knowledge of the fusion partners. We identified intergenic fusions involving driver genes, including PIK3CA, AKT3, RAF1 , and ESR1 , in 14% (24/173) of unselected patients with advanced HR+ breast cancer. FISH confirmed the corresponding chromosomal rearrangements in both primary and metastatic tumors. Expression of novel kinase fusions in nontransformed cells deregulates phosphoprotein signaling, cell proliferation, and survival in three-dimensional culture, whereas expression in HR+ breast cancer models modulates estrogen-dependent growth and confers hormonal therapy resistance in vitro and in vivo Strikingly, shorter overall survival was observed in patients with rearrangement-positive versus rearrangement-negative tumors...
March 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29202431/triple-negative-breast-cancer-emerging-therapeutic-modalities-and-novel-combination-therapies
#18
REVIEW
Alice Lee, Mustafa B A Djamgoz
Triple negative breast cancer (TNBC) is a complex and aggressive subtype of breast cancer which lacks oestrogen receptors, progesterone receptors and HER2 amplification, thereby making it difficult to target therapeutically. In addition, TNBC has the highest rates of metastatic disease and the poorest overall survival of all breast cancer subtypes. Resultantly, development of targeted therapies for TNBC is urgently needed. Recent efforts aimed at molecular characterisation of TNBCs have revealed various emerging therapeutic targets including PARP1, receptor and non-receptor tyrosine kinases, immune-checkpoints, androgen receptor and epigenetic proteins...
January 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29164972/molecular-subtyping-of-breast-cancer-improves-identification-of-both-high-and-low-risk-patients
#19
Maria Rossing, Olga Østrup, Wiktor W Majewski, Savvas Kinalis, Maj-Britt Jensen, Ann Knoop, Niels Kroman, Maj-Lis Talman, Thomas V O Hansen, Bent Ejlertsen, Finn C Nielsen
BACKGROUND: Transcriptome analysis enables classification of breast tumors into molecular subtypes that correlate with prognosis and effect of therapy. We evaluated the clinical benefits of molecular subtyping compared to our current diagnostic practice. MATERIALS AND METHODS: Molecular subtyping was performed on a consecutive and unselected series of 524 tumors from women with primary breast cancer (n = 508). Tumors were classified by the 256 gene expression signature (CIT) and compared to conventional immunohistochemistry (IHC) procedures...
January 2018: Acta Oncologica
https://www.readbyqxmd.com/read/29164968/characterization-of-basal-like-subtype-in-a-danish-consecutive-primary-breast-cancer-cohort
#20
Savvas Kinalis, Finn Cilius Nielsen, Maj-Lis Talman, Bent Ejlertsen, Maria Rossing
BACKGROUND: Transcriptome analysis enables classification of breast tumors into molecular subtypes. BRCA1/2 predisposed patients are more likely to suffer from a basal-like subtype and this group of patients displays a more distinct phenotype and genotype. Hence, in-depth characterization of this separate entity is needed. MATERIAL AND METHODS: Molecular subtyping was performed on a consecutive and unselected series of 1560 tumors from patients with primary breast cancer...
January 2018: Acta Oncologica
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