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https://www.readbyqxmd.com/read/28935542/phase-i-trial-of-veliparib-a-poly-adp-ribose-polymerase-inhibitor-plus-metronomic-cyclophosphamide-in-metastatic-her2-negative-breast-cancer
#1
Jesus Anampa, Alice Chen, John Wright, Margi Patel, Christine Pellegrino, Karen Fehn, Joseph A Sparano, Eleni Andreopoulou
BACKGROUND: Poly-ADP-ribose-polymerase is an essential nuclear enzyme, involved in base-excision repair of damaged DNA. Poly-ADP-ribose-polymerase inhibition sensitizes tumor cells to cytotoxic agents, which induce DNA damage, including cyclophosphamide (C), and metronomic dosing of C may optimize potential for synergy. METHODS: The primary objective of this phase I trial was to determine the safety and identify the recommended phase II dose of the combination of low-dose oral C (50, 75, 100, and 125 mg) once daily in combination with veliparib (V) (100, 200, and 300 mg) administered twice a day (BID) for 21-day cycles using a standard 3 + 3 design in patients with metastatic human epidermal growth factor receptor 2/neu-negative breast cancer...
September 1, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/28930807/breadth-of-genetic-testing-selected-by-patients-at-risk-of-hereditary-breast-and-ovarian-cancer
#2
J Brian Szender, Jasmine Kaur, Katherine Clayback, Mollie L Hutton, June Mikkelson, Kunle Odunsi, Cara Dresbold
OBJECTIVE: The aim of this study was to evaluate the ability of patients at risk of hereditary breast and ovarian cancer (HBOC) syndrome to select the extent of genetic testing personally preferred and the impact of demographic factors on the breadth of testing pursued. METHODS: A single-institution cohort was enumerated consisting of patients referred for clinical genetic counseling secondary to risk of HBOC syndrome. This was a retrospective study of consecutive patients seen for genetic counseling; all patients completed an epidemiologic questionnaire and provided personal and family medical histories...
September 19, 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28929593/efficacy-of-anthracycline-taxane-based-neo-adjuvant-chemotherapy-on-triple-negative-breast-cancer-in-brca1-brca2-mutation-carriers
#3
Lucie Bignon, Jean-Pierre Fricker, Catherine Nogues, Emmanuelle Mouret-Fourme, Dominique Stoppa-Lyonnet, Olivier Caron, Alain Lortholary, Laurence Faivre, Christine Lasset, Veronique Mari, Paul Gesta, Laurence Gladieff, Akila Hamimi, Thierry Petit, Michel Velten
This study aims to estimate the pathologic complete response (pCR) rate after neo-adjuvant chemotherapy and to compare disease-free survival (DFS) and overall survival (OS) between pCR and non-pCR groups of patients with triple-negative breast cancer (TNBC) and deleterious BRCA1 or BRCA2 mutation. We carried out a retrospective analysis of 53 patients including 46 BRCA1, 6 BRCA2, and 1 combined BRCA1 and BRCA2 mutation. All patients had been diagnosed with triple-negative breast cancer (TNBC) between 1997 and 2014...
September 19, 2017: Breast Journal
https://www.readbyqxmd.com/read/28925391/ezh2-contributes-to-the-response-to-parp-inhibitors-through-its-parp-mediated-poly-adp-ribosylation-in-breast-cancer
#4
H Yamaguchi, Y Du, K Nakai, M Ding, S-S Chang, J L Hsu, J Yao, Y Wei, L Nie, S Jiao, W-C Chang, C-H Chen, Y Yu, G N Hortobagyi, M-C Hung
Inhibitors against poly (ADP-ribose) polymerase (PARP) are promising targeted agents currently used to treat BRCA-mutant ovarian cancer and are in clinical trials for other cancer types, including BRCA-mutant breast cancer. To enhance the clinical response to PARP inhibitors (PARPis), understanding the mechanisms underlying PARPi sensitivity is urgently needed. Here, we show enhancer of zeste homolog 2 (EZH2), an enzyme that catalyzes H3 lysine trimethylation and associates with oncogenic function, contributes to PARPi sensitivity in breast cancer cells...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28918466/mutations-in-context-implications-of-brca-testing-in-diverse-populations
#5
Gabriela E S Felix, Yonglan Zheng, Olufunmilayo I Olopade
Cancer is a common non-communicable disease worldwide, although it exhibits differential population trends in incidence and mortality rates. The differences relate to population structure, environmental risk factors as well as health system organization. This article discusses the potential impact of genetic testing on population health, focusing in particular on the mutational spectrum of breast cancer susceptibility genes in diverse populations. We identify the need for improved access to, and increased investment in, comprehensive cancer risk assessment and genetic testing as well as cancer control measures that take into account lifestyle, environmental, and social factors in understudied minority groups...
September 16, 2017: Familial Cancer
https://www.readbyqxmd.com/read/28914396/the-expected-benefit-of-preventive-mastectomy-on-breast-cancer-incidence-and-mortality-in-brca-mutation-carriers-by-age-at-mastectomy
#6
Vasily Giannakeas, Steven A Narod
PURPOSE: Preventive breast surgery is offered to unaffected BRCA mutation carriers to prevent breast cancer incidence and mortality. The clinical benefit of preventive mastectomy can be measured in several ways, including extension of life expectancy (mean years of life gained) and by estimating the probability of surviving until age 80. We sought to estimate the expected benefit of a preventive mastectomy at various ages, using these indices of mortality, by simulating hypothetical cohorts of women...
September 15, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28903167/oncologic-safety-of-prophylactic-nipple-sparing-mastectomy-in-a-population-with-brca-mutations-a-multi-institutional-study
#7
James W Jakub, Anne Warren Peled, Richard J Gray, Rachel A Greenup, John V Kiluk, Virgilio Sacchini, Sarah A McLaughlin, Julia C Tchou, Robert A Vierkant, Amy C Degnim, Shawna Willey
Importance: Nipple-sparing mastectomy (NSM) offers superior cosmetic outcomes and has been gaining wide acceptance; however, its role among patients with BRCA mutations remains controversial. Objective: To report on the oncologic safety of NSM and provide evidence-based data to patients and health care professionals regarding preservation of the nipple-areolar complex during a risk-reducing mastectomy in a population with BRCA mutations. Design, Setting, and Participants: We retrospectively reviewed the outcomes of 9 institutions' experience with prophylactic NSM from 1968 to 2013 in a cohort of patients with BRCA mutations...
September 13, 2017: JAMA Surgery
https://www.readbyqxmd.com/read/28903158/surgeon-influence-on-variation-in-receipt-of-contralateral-prophylactic-mastectomy-for-women-with-breast-cancer
#8
Steven J Katz, Sarah T Hawley, Ann S Hamilton, Kevin C Ward, Monica Morrow, Reshma Jagsi, Timothy P Hofer
Importance: Rates of contralateral prophylactic mastectomy (CPM) have markedly increased but we know little about the influence of surgeons on variability of the procedure in the community. Objective: To quantify the influence of the attending surgeon on rates of CPM and clinician attitudes that explained it. Design, Setting, and Participants: In this population-based survey study, we identified 7810 women with stages 0 to II breast cancer treated in 2013 to 2015 through the Surveillance, Epidemiology, and End Results registries of Georgia and Los Angeles County...
September 13, 2017: JAMA Surgery
https://www.readbyqxmd.com/read/28893223/brca2-carriers-with-male-breast-cancer-show-elevated-tumour-methylation
#9
Siddhartha Deb, Kylie L Gorringe, Jia-Min B Pang, David J Byrne, Elena A Takano, kConFab Investigators, Alexander Dobrovic, Stephen B Fox
BACKGROUND: Male breast cancer (MBC) represents a poorly characterised group of tumours, the management of which is largely based on practices established for female breast cancer. However, recent studies demonstrate biological and molecular differences likely to impact on tumour behaviour and therefore patient outcome. The aim of this study was to investigate methylation of a panel of commonly methylated breast cancer genes in familial MBCs. METHODS: 60 tumours from 3 BRCA1 and 25 BRCA2 male mutation carriers and 32 males from BRCAX families were assessed for promoter methylation by methylation-sensitive high resolution melting in a panel of 10 genes (RASSF1A, TWIST1, APC, WIF1, MAL, RARβ, CDH1, RUNX3, FOXC1 and GSTP1)...
September 11, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28884397/brca1-gene-function-and-deficiency
#10
REVIEW
Miho Takaoka, Yoshio Miki
The BRCA1 protein, a hereditary breast and ovarian cancer-causing gene product, is known as a multifunctional protein that performs various functions in cells. It is well known, along with BRCA 2, to cause hereditary breast and ovarian cancer, but here we will specifically focus on BRCA1. We introduce the mechanism and the latest report on homologous recombination repair, replication, involvement in checkpoint regulation, transcription, chromatin remodeling, and cytoplasmic function (centrosome regulation, apoptosis, selective autophagy), and consider the possibility of carcinogenesis from inhibition of the intracellular functions in each...
September 7, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28881636/the-landscape-of-dna-methylation-mediated-regulation-of-long-non-coding-rnas-in-breast-cancer
#11
Chunlong Zhang, Xinyu Wang, Xuecang Li, Ning Zhao, Yihan Wang, Xiaole Han, Ce Ci, Jian Zhang, Meng Li, Yan Zhang
Although systematic studies have identified a host of long non-coding RNAs (lncRNAs) which are involved in breast cancer, the knowledge about the methyla-tion-mediated dysregulation of those lncRNAs remains limited. Here, we integrated multi-omics data to analyze the methylated alteration of lncRNAs in breast invasive carcinoma (BRCA). We found that lncRNAs showed diverse methylation patterns on promoter regions in BRCA. LncRNAs were divided into two categories and four subcategories based on their promoter methylation patterns and expression levels be-tween tumor and normal samples...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881597/tgfbeta-and-mirna-regulation-in-familial-and-sporadic-breast-cancer
#12
Katia Danza, Simona De Summa, Rosamaria Pinto, Brunella Pilato, Orazio Palumbo, Massimo Carella, Ondina Popescu, Maria Digennaro, Rosanna Lacalamita, Stefania Tommasi
The term 'BRCAness' was introduced to identify sporadic malignant tumors sharing characteristics similar to those germline BRCA-related. Among all mechanisms attributable to BRCA1 expression silencing, a major role has been assigned to microRNAs. MicroRNAs role in familial and sporadic breast cancer has been explored but few data are available about microRNAs involvement in homologous recombination repair control in these breast cancer subgroups. Our aim was to seek microRNAs associated to pathways underlying DNA repair dysfunction in breast cancer according to a family history of the disease...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881380/missed-therapeutic-and-prevention-opportunities-in-women-with-brca-mutated-epithelial-ovarian-cancer-and-their-families-due-to-low-referral-rates-for-genetic-counseling-and-brca-testing-a-review-of-the-literature
#13
Paul J Hoskins, Walter H Gotlieb
Answer questions and earn CME/CNE Fifteen percent of women with epithelial ovarian cancer have inherited mutations in the BRCA breast cancer susceptibility genes. Knowledge of her BRCA status has value both for the woman and for her family. A therapeutic benefit exists for the woman with cancer, because a new family of oral drugs, the poly ADP-ribose polymerase (PARP) inhibitors, has recently been approved, and these drugs have the greatest efficacy in women who carry the mutation. For her family, there is the potential to prevent ovarian cancer in those carrying the mutation by using risk-reducing surgery...
September 7, 2017: CA: a Cancer Journal for Clinicians
https://www.readbyqxmd.com/read/28880857/brca-genetic-testing-and-receipt-of-preventive-interventions-among-women-aged-18-64-years-with-employer-sponsored-health-insurance-in-nonmetropolitan-and-metropolitan-areas-united-states-2009-2014
#14
Katherine Kolor, Zhuo Chen, Scott D Grosse, Juan L Rodriguez, Ridgely Fisk Green, W David Dotson, M Scott Bowen, Julie A Lynch, Muin J Khoury
PROBLEM/CONDITION: Genetic testing for breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) gene mutations can identify women at increased risk for breast and ovarian cancer. These testing results can be used to select preventive interventions and guide treatment. Differences between nonmetropolitan and metropolitan populations in rates of BRCA testing and receipt of preventive interventions after testing have not previously been examined. PERIOD COVERED: 2009-2014...
September 8, 2017: MMWR. Surveillance Summaries: Morbidity and Mortality Weekly Report. Surveillance Summaries
https://www.readbyqxmd.com/read/28879638/impact-of-etoposide-on-brca1-expression-in-various-breast-cancer-cell-lines
#15
Xi Zhang, Simone Hofmann, Nadia Harbeck, Udo Jeschke, Sophie Sixou
Breast cancer 1 (BRCA1), as a tumor suppressor, exerts an effective influence on protecting DNA integrity to suppress the development of breast cancer (BC). BRCA1 expression is induced in response to DNA-damaging agents such as etoposide. Germline BRCA1 gene mutations are associated with development of hereditary BC. However, besides BRCA-mutated BCs, some sporadic cancers may also exhibit a BRCA-like phenotype, displaying so-called 'BRCAness'. This common phenotype may respond to similar therapeutic approaches as BRCA-mutated tumors and may thus have important implications for the clinical management of these cancers...
September 6, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28875097/sustained-long-term-maintenance-of-remission-with-single-agent-veliparib-in-recurrent-triple-negative-breast-cancer
#16
Karthik Kota, Shannon Puhalla
Triple-negative breast cancers (TNBC) have poorer outcomes than hormone positive or human epidermal growth factor receptor 2 (HER2)-positive breast cancers, with chemotherapy being the usual standard of care. Veliparib, a poly ADP-ribose polymerase (PARP) inhibitor, has been studied in both breast cancer susceptibility genes 1 and 2 (BRCA)-mutation related and sporadic cancers as a single agent and in combination with chemotherapy. Here, we describe a patient whose metastatic recurrence of TNBC was treated with combination chemotherapy and veliparib followed by maintenance single-therapy veliparib...
July 4, 2017: Curēus
https://www.readbyqxmd.com/read/28870960/risk-reducing-salpingo-oophorectomy-in-women-at-higher-risk-of-ovarian-and-breast-cancer-a-single-institution-prospective-series
#17
Enzo Ricciardi, Federica Tomao, Giovanni Aletti, Luca Bazzurini, Luca Bocciolone, Sara Boveri, Fabio Landoni, Maria Teresa Lapresa, Matteo Maruccio, Gabriella Parma, Fedro Peccatori, Maria Cristina Petrella, Vanna Zanagnolo, Nicoletta Colombo, Angelo Maggioni
BACKGROUND/AIM: Occult cancers' reported rates vary from 2-12% and serous tubal intraepithelial carcinomas (STICs) have been identified in 3-12% of the prophylactically removed tubes of women carrying a BRCA mutation. The aim of this study was to evaluate the incidence of tubal minor epithelial atypia (STIL), STIC, and occult invasive cancer and to evaluate the cancer-specific mortality in a prospective series of women at higher risk of ovarian and breast cancer undergoing risk-reducing salpingo-oophorectomy (RRSO) n a tertiary cancer center...
September 2017: Anticancer Research
https://www.readbyqxmd.com/read/28868023/next-generation-sequencing-in-order-to-better-characterize-a-brca-variant-of-uncertain-significance
#18
Steven Sorscher, Shakti Ramkissoon
BRCA germline mutations are the most common predisposing factor in familial breast-ovarian cancer syndrome families. However, many screened patients are identified as harboring BRCA variants of uncertain significance (VUS), rather than carrying deleterious germline mutations [Calo et al.: Cancers 2010; 2:1644-1660]. While such VUSs are typically reclassified as benign polymorphisms, this may occur years after the VUS is first identified [Murray et al.: Genet Med 2011; 13; 998-1005]. Loss of heterozygosity (LOH) of BRCA is nearly always the gatekeeper event in inherited BRCA-related breast cancer and LOH of BRCA is rare in sporadic cancers [Osorio et al...
May 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28856077/exceptional-responses-to-standard-therapy-in-a-patient-with-metastatic-her2-positive-breast-cancer
#19
Carsten Nieder, Bård Mannsåker, Ellinor Haukland
Patients with metastatic breast cancer involving the liver and brain often have short overall survival. Here, we report a case of de novo metastatic breast cancer with multiple liver metastases at initial diagnosis in February 2011 in a 35-year-old Caucasian female patient. The histology was poorly differentiated invasive ductal carcinoma (estrogen and progesterone receptor negative, HER2 positive) and the patient was negative for germline BRCA 1 and 2 mutations. Systemic therapy with trastuzumab and docetaxel was given for six months and then switched to trastuzumab only because of peripheral neuropathy...
June 29, 2017: Curēus
https://www.readbyqxmd.com/read/28842166/the-nurd-complex-mediated-p21-suppression-facilitates-chemoresistance-in-brca-proficient-breast-cancer
#20
Ming-Feng Hou, Chi-Wen Luo, Tsung-Ming Chang, Wen-Chun Hung, Tzu-Yi Chen, Ya-Li Tsai, Chee-Yin Chai, Mei-Ren Pan
The Mi-2/nucleosome remodeling and deacetylase (NuRD) complex play a role in silencing gene expression. CHD4, the core component of the NuRD complex, which cooperates with histone deacetylase in reducing tumor suppressor genes (TSGs). To dissect the mechanisms underlying cancer promotion, we clarify the role of CHD4 in cyclin-dependent kinase inhibitor protein p21. Here, our data indicates that CHD4 deficiency impairs the recruitments of HDAC1 to the p21 promoter. ~ 300bp proximal promoter region is responsible for CHD4-HDAC1 axis-mediated p21 transcriptional activity...
August 24, 2017: Experimental Cell Research
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