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Hélène Marijon, Dhong Hyun Lee, LingWen Ding, Haibo Sun, Sigal Gery, Aimery de Gramont, H Phillip Koeffler
PURPOSE: Despite similarities with BRCA-mutated breast cancers, triple-negative breast cancers (TNBC) remain resistant to poly(ADP-ribose) polymerase (PARP) inhibitors as single agents. Histone deacetylase inhibitors (HDACi) can decrease expression of proteins involved in DNA repair. We thus hypothesized that a HDACi (suberoylanilide hydroxamic acid (SAHA) or belinostat) could sensitize TNBC to the PARP inhibitor olaparib. METHODS: Human TNBC cells were co-treated with olaparib and either SAHA or belinostat, and their effects on survival, proliferation, cell cycle, apoptosis and DNA repair pathways were evaluated...
March 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Katherine Sullivan-Reed, Elisabeth Bolton-Gillespie, Yashodhara Dasgupta, Samantha Langer, Micheal Siciliano, Margaret Nieborowska-Skorska, Kritika Hanamshet, Elizaveta A Belyaeva, Andrea J Bernhardy, Jaewong Lee, Morgan Moore, Huaqing Zhao, Peter Valent, Ksenia Matlawska-Wasowska, Markus Müschen, Smita Bhatia, Ravi Bhatia, Neil Johnson, Mariusz A Wasik, Alexander V Mazin, Tomasz Skorski
PARP inhibitors (PARPis) have been used to induce synthetic lethality in BRCA-deficient tumors in clinical trials with limited success. We hypothesized that RAD52-mediated DNA repair remains active in PARPi-treated BRCA-deficient tumor cells and that targeting RAD52 should enhance the synthetic lethal effect of PARPi. We show that RAD52 inhibitors (RAD52is) attenuated single-strand annealing (SSA) and residual homologous recombination (HR) in BRCA-deficient cells. Simultaneous targeting of PARP1 and RAD52 with inhibitors or dominant-negative mutants caused synergistic accumulation of DSBs and eradication of BRCA-deficient but not BRCA-proficient tumor cells...
June 12, 2018: Cell Reports
Tayfun Toptas, Elif Pestereli, Tayup Simsek, Selen Bozkurt, Gulgun Erdogan, Seyda Karaveli
Aims: To investigate whether the presence of serous tubal intraepithelial carcinoma (STIC) is associated with clinical outcomes in a nonselected (unknown BRCA status) cohort of patients with a high-grade serous carcinoma (HGSC) of the ovary, fallopian tube, and peritoneum. Settings and Design: A prospective case-series with planned data collection. Subjects and Methods: The study was conducted in a total of 131 patients, who underwent primary cytoreductive surgery between 2007 and 2012...
April 2018: Journal of Cancer Research and Therapeutics
Shoko Vos, Paul Joannes van Diest, Cathy Beatrice Moelans
BACKGROUND: A considerable number of breast and ovarian carcinomas are due to underlying BRCA gene aberrations. Of these, BRCA germline mutations and BRCA promoter methylation are thought to be mutually exclusive, which could be exploited in clinical practice. However, this paradigm has not been studied extensively and systematically. OBJECTIVE: To systematically investigate to what extent BRCA promoter methylation has been reported in breast and ovarian carcinomas of BRCA germline mutation carriers...
July 2018: Critical Reviews in Oncology/hematology
Rui Jiang, Chunming Zhao, Binbin Gao, Jiawen Xu, Wei Song, Peng Shi
OBJECTIVE: This study aimed at finding the long non-coding RNA (lncRNA), miRNA and mRNA which played critical roles in breast cancer (BrCa) by using mixOmics R package. METHOD: The BrCa dataset were obtained from TCGA and then analyzed using "DESeq2" R package. Multivariate analyses were performed with the "mixOmics" R package and the first component of the stacked partial least-Squares discriminant analysis results were used for searching the interested lncRNA, miRNA and mRNA...
June 8, 2018: International Journal of Biochemistry & Cell Biology
(no author information available yet)
No abstract text is available yet for this article.
June 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
Domenica Lorusso, Elisa Tripodi, Giuseppa Maltese, Stefano Lepori, Ilaria Sabatucci, Giorgio Bogani, Francesco Raspagliesi
Epithelial ovarian cancer is the sixth most common cancer among women worldwide and the first cause of death among gynecological malignancies. Most of the patients present recurrent disease and unfortunately cannot be cured. The unsatisfactory results obtained with salvage chemotherapy have elicited investigators to search for novel biological agents capable of achieving a better control of the disease. In the setting of homologous recombination deficiency, the DNA errors that occur cannot be accurately repaired, and the treatment with poly(ADP-ribose) polymerase (PARP) inhibition results in definitive cell death in a process called synthetic lethality...
2018: Drug Design, Development and Therapy
Michael Untch, Rachel Würstlein, Norbert Marschner, Diana Lüftner, Doris Augustin, Susanne Briest, Johannes Ettl, Renate Haidinger, Lothar Müller, Volkmar Müller, Eugen Ruckhäberle, Nadia Harbeck, Christoph Thomssen
The fourth international advanced breast cancer consensus conference (ABC4) on the diagnosis and treatment of advanced breast cancer (ABC) headed by Professor Fatima Cardoso was once again held in Lisbon on November 2 - 4, 2017. To simplify matters, the abbreviation ABC will be used hereinafter in the text. In clinical practice, the abbreviation corresponds to metastatic breast cancer or locally far-advanced disease. This year the focus was on new developments in the treatment of ABC. Topics discussed included the importance of CDK4/6 inhibition in hormone receptor (HR)-positive ABC, the use of dual antibody blockade to treat HER2-positive ABC, PARP inhibition in triple-negative ABC and the potential therapeutic outcomes...
May 2018: Geburtshilfe und Frauenheilkunde
Claudio Vernieri, Alessia Mennitto, Michele Prisciandaro, Veronica Huber, Monica Milano, Lucia Rinaldi, Maria Silvia Cona, Claudia Maggi, Benvenuto Ferrari, Siranoush Manoukian, Gabriella Mariani, Giulia Bianchi, Giuseppe Capri, Licia Rivoltini, Filippo de Braud
Platinum salts are active against metastatic triple negative breast cancer (mTNBC), and biomarkers to predict their effectiveness are urgently needed. In recent years, the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) have emerged as prognostic biomarkers in many malignancies, but their predictive role in platinum-treated mTNBC patients remains unexplored. We performed a retrospective, single centre study to evaluate the association between baseline NLR or PLR and progression free survival (PFS) of mTNBC patients treated with platinum-based chemotherapy...
June 7, 2018: Scientific Reports
Yosr Hamdi, Maroua Boujemaa, Mariem Ben Rekaya, Cherif Ben Hamda, Najah Mighri, Houda El Benna, Nesrine Mejri, Soumaya Labidi, Nouha Daoud, Chokri Naouali, Olfa Messaoud, Mariem Chargui, Kais Ghedira, Mohamed Samir Boubaker, Ridha Mrad, Hamouda Boussen, Sonia Abdelhak
BACKGROUND: A family history of breast cancer has long been thought to indicate the presence of inherited genetic events that predispose to this disease. In North Africa, many specific epidemio-genetic characteristics have been observed in breast cancer families when compared to Western populations. Despite these specificities, the majority of breast cancer genetics studies performed in North Africa remain restricted to the investigation of the BRCA1 and BRCA2 genes. Thus, comprehensive data at a whole exome or whole genome level from local patients are lacking...
June 7, 2018: Journal of Translational Medicine
F Poggio, M Bruzzone, M Ceppi, N F Pondé, G La Valle, L Del Mastro, E de Azambuja, M Lambertini
Background: The role of platinum-based neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) patients is highly controversial and it is not endorsed by current guidelines. Our meta-analysis aimed to better elucidate its activity, efficacy and safety. Material and methods: A systematic search of Medline, Web of Science and conferences proceedings up to 30 October 2017 was carried out to identify randomized controlled trials (RCTs) investigating platinum-based versus platinum-free neoadjuvant chemotherapy in TNBC patients...
June 4, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Panagiotis A Konstantinopoulos, Ursula A Matulonis
PARP inhibitors have transformed treatment for ovarian cancer, a cancer notable for homologous recombination (HR) deficiencies and aberrant DNA repair, especially high grade serous subtype. PARP inhibitors are now approved for recurrent ovarian cancer as maintenance following response to platinum chemotherapy and BRCA mutated (BRCAm) cancer treatment.
June 5, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Xin Wang, Yaqin Shi, Doudou Huang, Xiaoxiang Guan
Inhibition of Poly (ADP-ribose) polymerase (PARP) has shown marked benefit for breast cancer with homologous recombination deficiency, whether driven by defects in BRCA1, BRCA2, or other pathway components. Since the initial approval of olaparib, a mostly investigated PARP inhibitor (PARPi), the clinical development of PARPi in breast cancer treatment has been a major emphasis. Researches in investigating platinum-PARPi combination use compared with platinum monotherapy demonstrated promising benefit in metastatic BRCA mutated breast cancer or TNBC, while no such superiority was observed in the neoadjuvant setting of TNBC...
May 31, 2018: Cancer Treatment Reviews
Carolyn S Wolf-Gould, Moira R Riley, Jeremi M Carswell
The risks of being a cisgender BRCA1/BRCA2 mutation carrier (BRCA1+/BRCA2+) are well documented, and recommendations to mitigate cancer risk in BRCA+ cisgender women are clear. However, there is a lack of guidance for BRCA+ transgender women. In this article, we discuss the case of a trans-feminine youth who presented at a gender clinic for medications for pubertal suppression and was identified as a BRCA1 mutation carrier. We explore principles of bioethics to consider when the potential risks of treatment are unclear...
May 2018: LGBT Health
Nadine M Tung, Judy E Garber
Testing for germline BRCA1/2 mutations has an established predictive role in breast cancer risk assessment. More recently, studies have also identified BRCA1/2 status as clinically relevant in the selection of therapy for patients already diagnosed with breast cancer. Emerging breast and ovarian cancer research indicate that BRCA status predicts responsiveness to platinum-based chemotherapy, as well as to inhibitors of poly(ADP-ribose) polymerase (PARP), owing to the ability of these interventions to inhibit DNA repair pathways...
June 5, 2018: British Journal of Cancer
Steven Sorscher
Choosing the optimal therapy for a patient's cancer has long been based on whether the cancer demonstrates a predictive marker of efficacy. The U.S. Food and Drug Administration (FDA) has now approved use of a targeted therapy based solely on tumor molecular markers (pembrolizumab for tumors with deficient mismatch repair [MMR] and high microsatellite instability [MSI]) and approved another therapy based solely on a germline mutation as the predictive marker of benefit (olaparib for BRCA carriers with ovarian or breast cancer) [New Engl J Med 2017;377:1409-1412, N Engl J Med 2012;366:1382-1392, N Eng J Med 2017;377:523-533]...
June 4, 2018: Oncologist
Thordis Jonsdottir, Heiddis Valdimarsdottir, Laufey Tryggvadottir, Sigrun Helga Lund, Marianna Thordardottir, Magnus Karl Magnusson, Unnur Valdimarsdottir
Introduction The aim of this study was to explore the attitudes of Icelandic women towards existing genetic information, genetic counseling and genetic testing for BRCA mutations which dramatically increase risk for aggressive cancers. Materials and methods Women attending the cancer prevention clinic in Reykjavik, capital of Iceland, from October 12th until November 20th 2015 received an invitation to participate. Participation involved answering a short online questionnaire about background, family history of cancer as well as attitudes towards genetic counseling, BRCA testing and preventive use of such information...
June 2018: Læknablađiđ
Oskar Thor Johannsson
No abstract text is available yet for this article.
June 2018: Læknablađiđ
Pnina Mor, Sarah Brennenstuhl, Kelly A Metcalfe
Women with a germline pathogenic variant in the BReast CAncer susceptibility genes (BRCA1 or BRCA2) have an increased risk of early-onset breast and ovarian cancer. In addition to weighing cancer screening and risk-reduction options, healthy BRCA mutation carriers of childbearing age may choose to preclude passing the mutation to the next generation. In the current study, we report on preimplantation genetic diagnosis (PGD) practices in BRCA-positive Israeli women who were offered PGD at no cost. METHODS: we measured PGD uptake, decision satisfaction or regret, and predictors of uptake...
June 1, 2018: Journal of Genetic Counseling
Julia Hollingsworth, Angela Lau, Alicia Tone, Alexandra Kollara, Lisa Allen, Terence J Colgan, Valerie Dube, Barry Rosen, K Joan Murphy, Ellen M Greenblatt, Tomer Feigenberg, Carl Virtanen, Theodore J Brown
Germline BRCA1 or BRCA2 mutations (mtBRCA1 and mtBRCA2) increase risk for high-grade serous ovarian cancer (HGSOC), the most commonly diagnosed epithelial ovarian cancer histotype. Other identified risk factors for this cancer, which originates primarily in the distal fallopian tube epithelium (FTE), implicate ovulation, during which the FTE cells become transiently exposed to follicular fluid (FF). To test whether mtBRCA1 or mtBRCA2 nonmalignant FTE cells respond differently to periovulatory FF exposure than control patient FTE cells, gene expression profiles from primary FTE cultures derived from BRCA1 or BRCA2 mutation carriers or control patients were compared at baseline, 24 hours after FF exposure, and 24 hours after FF replacement with culture medium...
May 28, 2018: Neoplasia: An International Journal for Oncology Research
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