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https://www.readbyqxmd.com/read/29232464/treatment-of-recurrent-ovarian-cancer
#1
S Pignata, S C Cecere, A Du Bois, P Harter, F Heitz
Despite optimal surgery and appropriate first-line chemotherapy, ∼70%-80% of patients with epithelial ovarian cancer will develop disease relapse. The same modalities as used primarily are available for treatment of recurrent ovarian cancer (ROC). The rationale for repetitive surgery in ROC was based on a stable body of retrospective data; however, prospective data were missing. Now, preliminary data from the prospective AGO-DESKTOP III give evidence that surgery for ROC seems to be of benefit for selected patients with platinum-sensitive relapse undergoing complete resection...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29228718/increased-single-strand-annealing-rather-than-non-homologous-end-joining-predicts-hereditary-ovarian-carcinoma
#2
Miriam Deniz, Tatiana Romashova, Sarah Kostezka, Anke Faul, Theresa Gundelach, Maria Moreno-Villanueva, Wolfgang Janni, Thomas W P Friedl, Lisa Wiesmüller
Mutations in genes encoding DNA double-strand break (DSB) repair components, especially homologous recombination (HR) proteins, were found to predispose to breast and ovarian cancer. Beyond high penetrance risk gene mutations underlying monogenic defects, low risk gene mutations generate polygenic defects, enlarging the fraction of individuals with a predisposing phenotype. DSB repair dysfunction opens new options for targeted therapies; poly (ADP-ribose) polymerase (PARP) inhibitors have been approved for BRCA-mutated and platinum-responsive ovarian cancers...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228641/brca-mutations-in-the-manifestation-and-treatment-of-ovarian-cancer
#3
REVIEW
Zimin Pan, Xing Xie
BRCA genes are important for the integrity and stability of genetic material and play key roles in repairing DNA breaks via high fidelity homologous recombination. BRCA mutations are known to predispose carriers to gynecological malignancies, accounting for a majority of hereditary OC cases. Known to be lethal, OC is difficult to detect and control. Testing for BRCA mutations is a key step in the risk assessment, prognosis, treatment and prevention of OC and current clinical guidelines recommend BRCA mutation testing for all OCs of epithelial origin...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29224898/clinical-outcome-of-patients-with-advanced-biliary-tract-cancer-in-a-dedicated-phase-i-unit
#4
R Sundar, A Custodio, A Petruckevich, M Chénard-Poirier, M Ameratunga, D Collins, J Lim, S B Kaye, N Tunariu, U Banerji, J de Bono, J Lopez
AIMS: Advanced biliary tract carcinomas (ABC) are malignancies with limited effective therapies for advanced disease. There is little published evidence of outcomes of ABC patients participating in phase I clinical trials. MATERIALS AND METHODS: Patient characteristics, treatment details and outcomes of ABC patients treated at a dedicated phase I unit were captured and analysed from case and trial records. RESULTS: In total, 123 ABC patients were included in the study, of which 48 patients participated in 41 different phase I trials; 75 (61%) did not participate due to rapid disease progression or patient choice...
December 7, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/29223478/phase-ii-trial-of-veliparib-in-patients-with-previously-treated-brca-mutated-pancreas-ductal-adenocarcinoma
#5
Maeve A Lowery, David P Kelsen, Marinela Capanu, Sloane C Smith, Jonathan W Lee, Zsofia K Stadler, Malcolm J Moore, Hedy L Kindler, Talia Golan, Amiel Segal, Hannah Maynard, Ellen Hollywood, MaryEllen Moynahan, Erin E Salo-Mullen, Richard Kinh Gian Do, Alice P Chen, Kenneth H Yu, Laura H Tang, Eileen M O'Reilly
PURPOSE: BRCA-associated cancers have increased sensitivity to poly(ADP-ribose) polymerase inhibitors (PARPis). This single arm, non-randomised, multicentre phase II trial evaluated the response rate of veliparib in patients with previously treated BRCA1/2- or PALB2-mutant pancreatic adenocarcinoma (PDAC). METHODS: Patients with stage III/IV PDAC and known germline BRCA1/2 or PALB2 mutation, 1-2 lines of treatment, Eastern Cooperative Oncology Group 0-2, were enrolled...
December 7, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29216337/brca-1-and-2-mutation-status-the-elephant-in-the-room-during-oncofertility-counseling-for-young-breast-cancer-patients
#6
S Paluch-Shimon, F A Peccatori
No abstract text is available yet for this article.
December 5, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29214031/parp-inhibitors-as-potential-therapeutic-agents-for-various-cancers-focus-on-niraparib-and-its-first-global-approval-for-maintenance-therapy-of-gynecologic-cancers
#7
REVIEW
Mekonnen Sisay, Dumessa Edessa
Poly (ADP-ribose) polymerases (PARPs) are an important family of nucleoproteins highly implicated in DNA damage repair. Among the PARP families, the most studied are PARP1, PARP2 and PARP 3. PARP1 is found to be the most abundant nuclear enzyme under the PARP series. These enzymes are primarily involved in base excision repair as one of the major single strand break (SSB) repair mechanisms. Being double stranded, DNA engages itself in reparation of a sub-lethal SSB with the aid of PARP. Moreover, by having a sister chromatid, DNA can also repair double strand breaks with either error-free homologous recombination or error-prone non-homologous end-joining...
2017: Gynecologic Oncology Research and Practice
https://www.readbyqxmd.com/read/29207007/fertility-preservation-in-women-harboring-deleterious-brca-mutations-ready-for-prime-time
#8
Fedro Alessandro Peccatori, Giorgia Mangili, Alice Bergamini, Francesca Filippi, Fabio Martinelli, Federica Ferrari, Stefania Noli, Emanuela Rabaiotti, Massimo Candiani, Edgardo Somigliana
Fertility issues have become critical in the management and counseling of BRCA mutation carriers. In this setting four points deserve consideration. (1) Women in general lose their ability to conceive at a mean age of 41 years, thus the suggested policy of prophylactic bilateral salpingo-oophorectomy at age 40 for BRCA mutation carriers does not affect the chances of natural pregnancy. Conversely, if the procedure is chosen at 35 years old, oocyte cryopreservation prior to surgery should be considered. (2) Some evidence suggests that ovarian reserve may actually be partly reduced in BRCA mutations carriers and that the mutation may affect ovarian responsiveness to stimulation...
December 1, 2017: Human Reproduction
https://www.readbyqxmd.com/read/29206279/the-risk-of-breast-cancer-in-brca1-and-brca2-mutation-carriers-without-a-first-degree-relative-with-breast-cancer
#9
K A Metcalfe, J Lubinski, J Gronwald, T Huzarski, J McCuaig, H T Lynch, B Karlan, W D Foulkes, C F Singer, S L Neuhausen, L Senter, A Eisen, P Sun, S A Narod
The objective of this study was to estimate the lifetime risk of breast cancer in women with a BRCA1 or BRCA2 mutation with and without at least one first-degree relative with breast cancer. A total of 2835 women with a BRCA1 or BRCA2 mutation were followed. Age- and gene-specific breast cancer rates were calculated. The relative risks of breast cancer for subjects with a family history of breast cancer, compared to no family history were calculated. The mean age at baseline was 41.1 years, and they were followed for a mean of 6...
December 5, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/29205122/parp-inhibitors-in-epithelial-ovarian-cancer
#10
Kristin N Taylor, Ramez N Eskander
Background Ovarian cancer remains the most common lethal gynecologic malignancy. The therapeutic gains with use of traditional cytotoxic chemotherapy in advanced stage disease remain limited, reflecting the need for novel therapies. Poly(ADP-ribose) polymerase (PARP) inhibitors have recently demonstrated a significant therapeutic effect in patients with recurrent, high grade serous ovarian cancer, both in the treatment of existing disease and in prolonging the disease-free interval. Objective The purpose of this article is to discuss PARP inhibitor use in patients with advanced stage ovarian cancer, and to extensively review the existing clinical literature and related patents...
December 3, 2017: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/29204512/brca-and-lynch-syndrome-associated-ovarian-cancers-behave-differently
#11
Neil A J Ryan, James Bolton, Rhona J McVey, D Gareth Evans, Emma J Crosbie
No abstract text is available yet for this article.
November 2017: Gynecologic Oncology Reports
https://www.readbyqxmd.com/read/29202431/triple-negative-breast-cancer-emerging-therapeutic-modalities-and-novel-combination-therapies
#12
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...
November 13, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29194191/brca-mutation-status-is-not-associated-with-increased-hematologic-toxicity-among-patients-undergoing-platinum-based-chemotherapy-for-ovarian-cancer
#13
Joanne Kotsopoulos, Karla Willows, Sandra Trat, Raymond H Kim, Alexandra Volenik, Ping Sun, Steven A Narod, Jeffrey Boyd, Taymaa May
OBJECTIVE: Women with an inherited BRCA1 or BRCA2 mutation may have an impaired ability to repair chemotherapy-induced damage as a result of a state of haploinsufficiency and may experience greater treatment-related toxicity. The objective of this study was to compare the hematologic adverse effect profiles associated with platinum-based chemotherapy in ovarian cancer patients with and without germline BRCA mutations. METHODS: We conducted a retrospective analysis of patients treated for high-grade serous ovarian cancer at Princess Margaret Cancer Center, Toronto, Ontario between January 2000 and December 2015...
November 30, 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/29193620/morphometric-study-of-adipocytes-on-breast-cancer-by-means-of-photonic-microscopy-and-image-analysis
#14
Luis Eduardo Suárez-Nájera, José Jorge Chanona-Pérez, Alejandra Valdivia-Flores, Daniel Marrero-Rodríguez, Mauricio Salcedo-Vargas, David Israel García-Ruiz, Marco Antonio Castro-Reyes
Worldwide, breast cancer (BrCa) is currently the leading cause of deaths associated to malignant lesions in adult women. Given that some studies have mentioned that peritumoral adipocytes may contribute to breast carcinogenesis, present work sought to quantitative evaluate the morphometry of these cells in a group of adult women. Three thousand six hundred sixty four breast adipocytes, that came from biopsies of a group of adult females with different types of breast carcinomas (ductal, lobular, and mixed) and one with normal tissues, were evaluated through an image analysis (IA) process regarding six morphometric descriptors: area (A), perimeter (P), Feret diameter (FD ), aspect ratio (AR), roundness factor (RF), and fractal dimension of cellular contour (FDC )...
November 27, 2017: Microscopy Research and Technique
https://www.readbyqxmd.com/read/29191972/mutations-in-homologous-recombination-genes-and-outcomes-in-ovarian-carcinoma-patients-in-gog-218-an-nrg-oncology-gynecologic-oncology-group-study
#15
Barbara M Norquist, Mark F Brady, Maria I Harrell, Tom Walsh, Ming K Lee, Suleyman Gulsuner, Sarah S Bernards, Silvia Casadei, Robert A Burger, Krishnansu S Tewari, Floor J Backes, Robert S Mannel, Gretchen Glaser, Cheryl Bailey, Stephen C Rubin, John T Soper, Heather A Lankes, Nilsa C Ramirez, Mary-Claire King, Michael J Birrer, Elizabeth M Swisher
PURPOSE: We hypothesized that mutations in homologous recombination repair (HRR) genes beyond BRCA1 and BRCA2 improve outcomes for ovarian carcinoma (OC) patients treated with platinum therapy and would impact the relative benefit of adding prolonged bevacizumab.  Experimental Design: We sequenced DNA from blood and/or neoplasm from 1,195 women enrolled in GOG-0218, a randomized phase III trial in advanced OC of bevacizumab added to carboplatin and paclitaxel. Defects in HRR were defined as damaging mutations in 16 genes...
November 30, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29187427/the-role-of-the-androgen-receptor-signaling-in-breast-malignancies
#16
REVIEW
Panagiotis F Christopoulos, Nikolaos I Vlachogiannis, Christiana T Vogkou, Michael Koutsilieris
Breast cancer (BrCa) is the most common malignancy among women worldwide, and one of the leading causes of cancer-related deaths in females. Despite the development of novel therapeutic modalities, triple-negative breast cancer (TNBC) remains an incurable disease. Androgen receptor (AR) is widely expressed in BrCa and its role in the disease may differ depending on the molecular subtype and the stage. Interestingly, AR has been suggested as a potential target candidate in TNBC, while sex hormone levels may regulate the role of AR in BrCa subtypes...
December 2017: Anticancer Research
https://www.readbyqxmd.com/read/29185120/characterization-of-a-novel-germline-brca1-splice-variant-c-5332-4dela
#17
Ciyu Yang, Sowmya Jairam, Kimberly A Amoroso, Mark E Robson, Michael F Walsh, Liying Zhang
PURPOSE: Germline mutations in BRCA1 and BRCA2 confer a significant increase in risk for cancer, and determining pathogenicity of a BRCA variant can guide the clinical management of the disease. About 1/3 of BRCA1 variants reported in the public databases have uncertain clinical significance due to lack of conclusive evidence. This study aims to characterize a novel BRCA1 deletion affecting the + 4 splice donor site identified in an individual with early-onset breast cancer. METHODS: The effect of BRCA1 c...
November 28, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29182397/breast-tissue-density-change-after-oophorectomy-in-brca-mutation-carrier-patients-using-visual-volumetric-analysis
#18
Augustin Lecler, Ariane Dunant, Suzette Delaloge, Delphine Wehrer, Tania Moussa, Olivier Caron, Corinne Balleyguier
OBJECTIVE: BRCA1/2 mutations account for 30-50% of hereditary breast cancers and bilateral oophorectomy is associated with a reduced risk of breast cancer (BC) in these patients. Breast density is a well-established BC risk factor and is also associated with increased risk in BRCA carriers. The aim of the study was to evaluate the impact of oophorectomy on mammographic breast density and to assess which method of breast density assessment is more sensitive to change over time. METHODS: Retrospective study of 50 BRCA1/2 patients who underwent bilateral oophorectomy and had at least a baseline and post-surgery mammogram...
November 28, 2017: British Journal of Radiology
https://www.readbyqxmd.com/read/29180466/synthetic-lethality-of-parp-inhibitors-in-combination-with-myc-blockade-is-independent-of-brca-status-in-triple-negative-breast-cancer
#19
Jason Pw Carey, Cansu Karakas, Tuyen Bui, Xian Chen, Smruthi Vijayaraghavan, Yang Zhao, Jing Wang, Keith Mikule, Jennifer K Litton, Kelly K Hunt, Khandan Keyomarsi
PARP inhibitors (PARPi) benefit only a fraction of breast cancer patients. Several of those patients exhibit intrinsic/acquired resistance mechanisms that limit efficacy of PARPi monotherapy. Here we show how the efficacy of PARPi in triple-negative breast cancers (TNBC) can be expanded by targeting MYC-induced oncogenic addiction. In BRCA-mutant/sporadic TNBC patients, amplification of the MYC gene is correlated with increased expression of the homologous DNA recombination enzyme RAD51 and tumors overexpressing both genes are associated with worse overall survival...
November 27, 2017: Cancer Research
https://www.readbyqxmd.com/read/29177190/functional-germline-variants-as-potential-co-oncogenes
#20
REVIEW
Divyansh Agarwal, Christoph Nowak, Nancy R Zhang, Lajos Pusztai, Christos Hatzis
Germline variants that affect the expression or function of proteins contribute to phenotypic variation in humans and likely determine individual characteristics and susceptibility to diseases including cancer. A number of high penetrance germline variants that increase cancer risk have been identified and studied, but germline functional polymorphisms are not typically considered in the context of cancer biology, where the focus is primarily on somatic mutations. Yet, there is evidence from familial cancers indicating that specific cancer subtypes tend to arise in carriers of high-risk germline variants (e...
2017: NPJ Breast Cancer
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