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https://www.readbyqxmd.com/read/29146938/computational-investigation-of-homologous-recombination-dna-repair-deficiency-in-sporadic-breast-cancer
#1
Yue Wang, Matthew H Ung, Sharon Cantor, Chao Cheng
BRCAness has important implications in the management and treatment of patients with breast and ovarian cancer. In this study, we propose a computational framework to measure the BRCAness of breast and ovarian tumor samples based on their gene expression profiles. We define a characteristic profile for BRCAness by comparing gene expression differences between BRCA1/2 mutant familial tumors and sporadic breast cancer tumors while adjusting for relevant clinical factors. With this BRCAness profile, our framework calculates sample-specific BRCA scores, which indicates homologous recombination (HR)-mediated DNA repair pathway activity of samples...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138572/current-status-of-poly-adp-ribose-polymerase-inhibitors-and-future-directions
#2
REVIEW
Akihiro Ohmoto, Shinichi Yachida
Inhibitors of poly(ADP-ribose) polymerases (PARPs), which play a key role in DNA damage/repair pathways, have been developed as antitumor agents based on the concept of synthetic lethality. Synthetic lethality is the idea that cell death would be efficiently induced by simultaneous loss of function of plural key molecules, for example, by exposing tumor cells with inactivating gene mutation of BRCA-mediated DNA repair to chemically induced inhibition of PARPs. Indeed, three PARP inhibitors, olaparib, rucaparib and niraparib have already been approved in the US or Europe, mainly for the treatment of BRCA-mutant ovarian cancer...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29128106/who-are-the-long-term-survivors-of-high-grade-serous-ovarian-cancer
#3
REVIEW
Claire Hoppenot, Mark A Eckert, Samantha M Tienda, Ernst Lengyel
Although the median survival for epithelial ovarian cancer (EOC) is <5years, approximately 15% of patients will survive for >10years. A better understanding of these exceptional responders could reveal opportunities to improve the dismal prognosis of most EOC patients. In this review, we examine the clinical and genomic features that have been associated with long-term survival, which is generally defined as survival of >7-10years after initial diagnosis. Clinical features influencing long-term survival have been best reported in large retrospective population-based studies...
November 8, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/29126396/feasibility-of-structured-endurance-training-and-mediterranean-diet-in-brca1-and-brca2-mutation-carriers-an-interventional-randomized-controlled-multicenter-trial-libre-1
#4
Marion Kiechle, Ricarda Dukatz, Maryam Yahiaoui-Doktor, Anika Berling, Maryam Basrai, Vera Staiger, Uwe Niederberger, Nicole Marter, Jacqueline Lammert, Sabine Grill, Katharina Pfeifer, Kerstin Rhiem, Rita K Schmutzler, Matthias Laudes, Michael Siniatchkin, Martin Halle, Stephan C Bischoff, Christoph Engel
BACKGROUND: Women with pathogenic BRCA germline mutations have an increased risk for breast and ovarian cancer that seems to be modified by life-style factors. Though, randomized trials investigating the impact of lifestyle interventions on cancer prevention and prognosis in BRCA carriers are still missing. METHODS: We implemented a multicenter, prospective randomized controlled trial in BRCA1/2 patients, comparing a lifestyle intervention group (IG) with a control group (CG) with the primary aim to prove feasibility...
November 10, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29109859/candidate-synthetic-lethality-partners-to-parp-inhibitors-in-the-treatment-of-ovarian-clear-cell-cancer
#5
Naoki Kawahara, Kenji Ogawa, Mika Nagayasu, Mai Kimura, Yoshikazu Sasaki, Hiroshi Kobayashi
Inhibitors of poly(ADP-ribose) polymerase (PARP) are new types of personalized treatment of relapsed platinum-sensitive ovarian cancer harboring BRCA1/2 mutations. Ovarian clear cell cancer (CCC), a subset of ovarian cancer, often appears as low-stage disease with a higher incidence among Japanese. Advanced CCC is highly aggressive with poor patient outcome. The aim of the present study was to determine the potential synthetic lethality gene pairs for PARP inhibitions in patients with CCC through virtual and biological screenings as well as clinical studies...
November 2017: Biomedical Reports
https://www.readbyqxmd.com/read/29096890/breast-cancer-epidemiology-prevention-and-screening
#6
Stella Winters, Charmaine Martin, Daniel Murphy, Navkiran K Shokar
Globally, breast cancer is both the most commonly occurring cancer and the commonest cause of cancer death among women. Available data suggest that incidence and mortality in high-resource countries has been declining whereas incidence and mortality in low-resource countries has been increasing. This pattern is likely to be due to changing risk factor profiles and differences in access to breast cancer early detection and treatment. Risk factors for breast cancer include increasing age, race, menarche history, breast characteristics, reproductive patterns, hormone use, alcohol use, tobacco use, diet, physical activity, and body habitus...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/29081841/niraparib-in-ovarian-cancer-results-to-date-and-clinical-potential
#7
REVIEW
Davide Caruso, Anselmo Papa, Silverio Tomao, Patrizia Vici, Pierluigi Benedetti Panici, Federica Tomao
Ovarian cancer is the first cause of death from gynaecological malignancy. Germline mutation in BRCA1 and 2, two genes involved in the mechanisms of reparation of DNA damage, are showed to be related with the incidence of breast and ovarian cancer, both sporadic and familiar. PARP is a family of enzymes involved in the base excision repair (BER) system. The introduction of inhibitors of PARP in patients with BRCA-mutated ovarian cancer is correlated with the concept of synthetic lethality. Among the PARP inhibitors introduced in clinical practice, niraparib showed interesting results in a phase III trial in the setting of maintenance treatment in ovarian cancer, after platinum-based chemotherapy...
September 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29069866/germline-mutations-in-pancreatic-cancer-and-potential-new-therapeutic-options
#8
REVIEW
Rille Pihlak, Juan W Valle, Mairéad G McNamara
Due to short-lived treatment responses in unresectable disease, pancreatic ductal adenocarcinoma (PDAC) continues to be one of the deadliest cancers. There is availability of new information about germline and sporadic mutations in the deoxyribonucleic acid (DNA) damage repair pathway in PDAC in recent decades and the expectation is that novel targeted therapies will thus be developed. A variety of germline mutations (BRCA2, BRCA1, PALB2, CDKN2A, ATM, TP53 and mismatch repair genes MLH1, MSH2, MSH6) have been reported in these patients with the highest prevalence being BRCA1/2...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29063517/parp-inhibitors-in-the-treatment-of-triple-negative-breast-cancer
#9
REVIEW
Jill J J Geenen, Sabine C Linn, Jos H Beijnen, Jan H M Schellens
Breast cancer is a heterogeneous disease, manifesting in a broad differentiation in phenotypes and morphologic profiles, resulting in variable clinical behavior. Between 10 and 20% of all breast cancers are triple negative. Triple-negative breast cancer (TNBC) lacks the expression of human epidermal growth factor receptor 2 (HER2) and hormone receptors; therefore, to date, chemotherapy remains the backbone of treatment. TNBC tends to be aggressive and has a high histological grade, resulting in a poor 5-year prognosis...
October 23, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29061774/immune-checkpoint-inhibitors-in-gynecological-cancers-update-of-literature-and-perspectives-of-clinical-research
#10
REVIEW
Angiolo Gadducci, Maria Elena Guerrieri
The presence of tumor infiltrating lymphocytes (TILs) influences the clinical outcome of cancer patients and immune checkpoint inhibitors (ICPI) have been approved for treating different types of malignancies. In this review, we assess the scanty data from literature and the perspectives of clinical research about the use of ICPI in gynecological cancers. These agents have obtained objective response rates ranging from 5.9% to 15% in early phase Ib-II trials, including patients with platinum-resistant ovarian cancer, whereas only anecdotal data are available for patients with recurrent, heavily pretreated endometrial cancer...
November 2017: Anticancer Research
https://www.readbyqxmd.com/read/29061375/evaluation-of-a-next-generation-sequencing-assay-for-brca1-and-brca2-mutation-detection
#11
Gabriele Lorenzo Capone, Anna Laura Putignano, Sharon Trujillo Saavedra, Irene Paganini, Roberta Sestini, Francesca Gensini, Irene De Rienzo, Laura Papi, Berardino Porfirio
The efficiency of a novel targeted next-generation sequencing (NGS) test, the Devyser BRCA kit, for a comprehensive analysis of all 48 coding exons of the high-risk breast/ovarian cancer susceptibility genes BRCA1 and BRCA2 has been assessed. The new assay intended to detect nucleotide substitutions, small deletions/insertions, and large deletions/duplications. To document the false-negative and false-positive rates of the NGS assay in the hands of end-users, 48 samples with previously identified 444 small-size variants and seven gross rearrangements were analyzed, showing 100% concordance with gold standards...
October 20, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/29058922/-satisfaction-and-overall-quality-of-life-in-brca-positive-women-after-prophylactic-surgeries
#12
P Šašková, D Pavlišta, L Dostálek
INTRODUCTION: Genetic mutations are responsible for 5-10% of all breast and ovarian carcinomas, while most of them are caused by a mutation of the BRCA gene. Women with this type of mutation have a lifetime risk of breast and ovarian cancer and therefore, they require very intensive medical care, including surgical prevention. Specifically, prophylactic bilateral mastectomy and prophylactic salpingo-oophorectomy are done, which undoubtedly decrease the riskof cancer. The aim of this review article is to inform healthcare professionals and the general public about the satisfaction of BRCA positive women with their decision to undergo these prophylactic surgeries, and also about the impact of these procedures on sexuality, menopausal symptoms, mental health and the overall quality of life...
2017: Rozhledy V Chirurgii: Měsíčník Československé Chirurgické Společnosti
https://www.readbyqxmd.com/read/29054544/-abnormalities-of-dna-repair-and-gynecological-cancers
#13
REVIEW
Aurélie Auguste, Alexandra Leary
The demonstration of frequent defects in the DNA damage response in high grade ovarian cancer has paved the way for a new therapeutic approach aimed at exploiting this unique vulnerability. The efficacy of poly (ADP) ribose polymerase inhibitors (PARPi) in patients with homologous recombination (HR) DNA repair deficient ovarian cancer (OC) resulting from a BRCA1/2 mutation has provided the proof of concept for synthetic lethality. Thus, olaparib is now approved by the EMA as maintenance therapy after response to a platinum regimen for patients with recurrent, platinum-sensitive, high-grade serous, BRCA1/2-mutated ovarian cancer...
October 17, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/29045555/reproductive-potential-and-performance-of-fertility-preservation-strategies-in-brca-mutated-breast-cancer-patients
#14
M Lambertini, O Goldrat, A R Ferreira, J Dechene, H A Azim, J Desir, A Delbaere, M-D t'Kint de Roodenbeke, E de Azambuja, M Ignatiadis, I Demeestere
BackgroundPreclinical evidence suggests a possible negative impact of deleterious BRCA mutations on female fertility. However, limited and rather conflicting clinical data are available. This study assessed the reproductive potential and performance of fertility preservation strategies in BRCA-mutated breast cancer patients.Patients and MethodsThis was a retrospective analysis of two prospective studies investigating oocyte cryopreservation and ovarian tissue cryopreservation in newly diagnosed early breast cancer patients...
October 10, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29040190/novel-therapeutics-for-ovarian-cancer-the-11th-biennial-rivkin-center-ovarian-cancer-research-symposium
#15
Neil Johnson, John B Liao
OBJECTIVE: The aim of this study was to summarize developments in novel therapeutics for ovarian cancer presented at the Ovarian Cancer Research Symposium held at the University of Washington. METHODS: A symposium of the leaders in ovarian cancer research was convened to present and discuss current advances and future directions in ovarian cancer research. RESULTS: The fourth session was held on September 13, 2016, and focused on Novel Therapeutics for Ovarian Cancer...
October 17, 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/29028552/risk-reducing-salpingo-oophorectomy-in-brca1-and-brca2-mutated-patients-an-evidence-based-approach-on-what-women-should-know
#16
REVIEW
F De Felice, C Marchetti, S M Boccia, A Romito, C M Sassu, M G Porpora, L Muzii, V Tombolini, P Benedetti Panici
This review is focused on the ovarian cancer risk reduction management in BRCA mutation carriers and is intended to assist with clinical decision-making. Obviously, treatment decisions must be based on the available evidence. Despite risk-reducing salpingo-oophorectomy is firmly recommended, several separate questions can be raised to address the variety of intense controversy of this approach. A special emphasis lies in the effective preventive surgical measure against ovarian cancer risk, in an attempt to detect the optimal timing and mitigate the impact on patients...
September 28, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29020822/trabectedin-mechanism-of-action-and-platinum-resistance-molecular-rationale
#17
Isabelle Ray-Coquard
Trabectedin presents a complex mode of action affecting key cell biology processes in tumor cells and in the tumor microenvironment. In ovarian cancer patients with a platinum treatment-free interval of 6-12 months treated with trabectedin + pegylated liposomal doxorubicin (PLD) or single-agent PLD, and retreated with platinum after relapse, overall survival was significantly prolonged in the trabectedin + PLD group. Mechanisms by which trabectedin restores tumor sensitivity to platinum include its interaction with components of the nucleotide excision repair machinery in tumor cells and inhibition of inflammatory mediators such as IL-6 in the tumor microenvironment...
October 11, 2017: Future Oncology
https://www.readbyqxmd.com/read/29020819/update-on-relapsed-ovarian-cancer-treatment-from-new-consensus-to-daily-clinical-practice
#18
Antonio González-Martín
The outcome of the 5th Ovarian Cancer Consensus Conference (OCCC) held in November 2015 in Tokyo, Japan, was the development of new and revised consensus statements to guide clinical investigations in ovarian cancer. The OCCC statements may also have direct application to daily clinical practice. This review examines the consensus statements for recurrent ovarian cancer and their impact on treatment paradigms. Importantly, patients are no longer to be categorized by the platinum-free interval (with its arbitrary 6-month cut-off points) but according to the question: 'is platinum still an option for the patient?' Another important change since the 4th OCCC in 2010 is the inclusion of BRCA mutation status when defining patient subgroups for entry into clinical trials...
October 11, 2017: Future Oncology
https://www.readbyqxmd.com/read/29019095/cost-effectiveness-of-surveillance-and-prevention-strategies-in-brca1-2-mutation-carriers
#19
Hideko Yamauchi, Chizuko Nakagawa, Makoto Kobayashi, Yusuke Kobayashi, Toshiki Mano, Seigo Nakamura, Masami Arai
BACKGROUND: Cost-effectiveness analysis is an important aspect of healthcare, including in Japan, where preventive measures for BRCA1/2 mutation carriers are not covered by health insurance. METHODS: We developed Markov models in a simulated cohort of women aged 35-70 years, and compared outcomes of surveillance with risk-reducing mastectomy (RRM) at age 35, risk-reducing salpingo-oophorectomy (RRSO) at age 45, and both (RRM&RRSO). We used breast and ovarian cancer incidences and adverse event rates from the previous studies, adjuvant chemotherapy, and hormonal therapy rates from the Hereditary Breast and Ovarian Cancer Registration 2015 in Japan, mortality rates from the National Cancer Center Hospital, Japan Society of Clinical Oncology, and Ministry of Health, Labour and Welfare, and direct costs from St...
October 10, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28989926/brca1-mutated-ovarian-cancer-with-skin-metastasis-a-case-report
#20
So Ra Oh, Jung-Woo Park, Hyun Young Kwon, Seo-Hee Rha
The major risk factor for ovarian cancer (OC) is mutation of the BRCA1 or BRCA2 DNA mismatch repair genes, which occurs in approximately 10% of OC cases. Most previous studies have demonstrated that BRCA1- and BRCA2-mutated OCs are associated with better prognosis than sporadic OCs. However, information about the patterns and clinical course of the metastatic spread of BRCA-mutated OCs is limited. Herein, we describe a case of OC with a BRCA1 mutation and skin metastases in a 49-year-old patient, which to the best of our knowledge has not been reported previously...
September 2017: Obstetrics & Gynecology Science
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