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Marie Eliade, Jeremy Skrzypski, Amandine Baurand, Caroline Jacquot, Geoffrey Bertolone, Catherine Loustalot, Charles Coutant, France Guy, Pierre Fumoleau, Yannis Duffourd, Laurent Arnould, Alexandra Delignette, Marie-Martine Padéano, Côme Lepage, Géraldine Raichon-Patru, Axelle Boudrant, Marie-Christine Bône-Lépinoy, Anne-Laure Villing, Aurélie Charpin, Karine Peignaux, Sandy Chevrier, Frédérique Vegran, François Ghiringhelli, Romain Boidot, Nicolas Sevenet, Sarab Lizard, Laurence Faivre
Until recently, the molecular diagnosis of hereditary breast and ovarian cancer (HBOC) was mostly based on BRCA1/2 testing. Next generation sequencing and the recent discovery of new genes involved in HBOC now permit the transfer of genomic capture targeting multiple candidate genes from research to clinical use. However, the implications for the management of patients and their families have not been extensively studied, in particular since some of these genes are not well-established cancer predisposing genes...
October 15, 2016: Oncotarget
Stephanie McGregor, James McElherne, Agata Minor, Jennifer Keller-Ramey, Ryan Dunning, Aliya N Husain, Wickii Vigneswaran, Carrie Fitzpatrick, Thomas Krausz
BRCA-associated protein 1 (BAP1) immunohistochemistry (IHC) and CDKN2A (p16) fluorescence in situ hybridization (FISH) have shown clinical utility in confirming the diagnosis of malignant pleural mesothelioma (MPM), but the role for using these two markers to guide clinical management is not yet clear. While p16 loss is predictive of poor prognosis, there is controversy as to whether BAP1 loss is predictive of a more favorable prognosis; how these results interact with one another has not been explored. We performed CDKN2A FISH on a previously published tissue microarray on which we had performed BAP1 IHC, revealing combined BAP1/p16 status for 93 MPM cases...
October 19, 2016: Human Pathology
Touria Derkaoui, Joaira Bakkach, Mohamed Mansouri, Ali Loudiyi, Mohamed Fihri, Fatima Zahra Alaoui, Amina Barakat, Bouchra El Yemlahi, Hassan Bihri, Naima Ghailani Nourouti, Mohcine Bennani Mechita
BACKGROUND: Triple Negative Breast Cancer (TNBC) is defined by a lack of estrogen and progesterone receptor gene expression and by the absence of overexpression on HER2. It is associated to a poor prognosis. We propose to analyze the clinicopathologic and prognostic characteristics of this breast cancer subtype in a Mediterranean population originated or resident in the North of Morocco. METHODS: We conducted a retrospective study of 279 patients diagnosed with breast cancer between January 2010 and January 2015...
October 22, 2016: BMC Women's Health
Fabrice Kwiatkowski, Pascal Dessenne, Claire Laquet, Jean-Pierre Daures, Mathilde Gay-Bellile, Yves-Jean Bignon
BACKGROUND: Young women exposed to a high hereditary breast and ovarian cancer (HBOC) risk are particularly vulnerable. They are ignored by health prevention measures but exposed to a stream of contradictory information (medicine, media, Internet). They may feel concerned about surgical prevention issues at a key moment of their identity construction (self, relationship, sexuality). We designed a special psychoeducational intervention to help these women cope better with these difficulties...
October 21, 2016: Trials
David J Pulford, Philipp Harter, Anne Floquet, Catherine Barrett, Dong Hoon Suh, Michael Friedlander, José Angel Arranz, Kosei Hasegawa, Hiroomi Tada, Peter Vuylsteke, Mansoor R Mirza, Nicoletta Donadello, Giovanni Scambia, Toby Johnson, Charles Cox, John K Chan, Martin Imhof, Thomas J Herzog, Paula Calvert, Pauline Wimberger, Dominique Berton-Rigaud, Myong Cheol Lim, Gabriele Elser, Chun-Fang Xu, Andreas du Bois
BACKGROUND: The focus on translational research in clinical trials has the potential to generate clinically relevant genetic data that could have importance to patients. This raises challenging questions about communicating relevant genetic research results to individual patients. METHODS: An exploratory pharmacogenetic analysis was conducted in the international ovarian cancer phase III trial, AGO-OVAR 16, which found that patients with clinically important germ-line BRCA1/2 mutations had improved progression-free survival prognosis...
October 21, 2016: BMC Medical Ethics
Violeta Régnier Galvão, Elizabeth Phillips, Pedro Giavina-Bianchi, Mariana C Castells
No abstract text is available yet for this article.
October 17, 2016: Journal of Allergy and Clinical Immunology in Practice
Leendert H Zaaijer, Helena C van Doorn, Marian J E Mourits, Marc van Beurden, Joanne A de Hullu, Muriel A Adank, Luc R C W van Lonkhuijzen, Hans F A Vasen, Brigitte F M Slangen, Katja N Gaarenstroom, Ronald P Zweemer, Peggy M L H Vencken, Caroline Seynaeve, Mieke Kriege
BACKGROUND: It is unknown whether a history of breast cancer (BC) affects the outcome of BRCA1/2-associated epithelial ovarian cancer (EOC). This was investigated in the current analysis. METHODS: We included 386 BRCA1/2-associated EOC patients diagnosed between 1980 and 2015. Progression-free survival (PFS), progression-free interval (PFI), overall survival (OS) and ovarian cancer-specific survival (OCSS) were compared between EOC patients with and without previous BC...
October 18, 2016: British Journal of Cancer
Raksha Rao, Renelle Pointdujour-Lim, Arupa Ganguly, Carol L Shields
PURPOSE: To report a case of unilateral multifocal melanoma in a patient with germ line BRCA-associated protein 1 mutation. METHODS: Case report. RESULTS: A 67-year-old white woman with a family history of lung and liver cancers developed blurred visual acuity of 20/30 in the left eye. She was discovered to have two independent pigmented choroidal melanomas in the macula and superotemporally, both demonstrating overlying subretinal fluid and orange pigment...
October 4, 2016: Retinal Cases & Brief Reports
Zora Baretta, Simone Mocellin, Elena Goldin, Olufunmilayo I Olopade, Dezheng Huo
BACKGROUND: The contribution of BRCA germline mutational status to breast cancer patients' prognosis is unclear. We aimed to systematically review and perform meta-analysis of the available evidence of effects of BRCA germline mutations on multiple survival outcomes of breast cancer patients as a whole and in specific subgroups of interest, including those with triple negative breast cancer, those with Ashkenazi Jewish ancestry, and patients with stage I-III disease. METHODS: Sixty studies met all inclusion criteria and were considered for this meta-analysis...
October 2016: Medicine (Baltimore)
Trevor Tejada-Bergés
As health care providers, we play a crucial role in the assessment of a patient's risk for hereditary breast cancer syndromes. The panorama of genetic assessment and testing has evolved dramatically since the identification of the BRCA genes. Next-generation sequencing technology has facilitated the development of multigene panels, but 1 consequence has been an increased identification of pathogenic variants at odds with a family history as well as variants of uncertain significance for which treatment guidelines are not defined...
October 5, 2016: Clinical Obstetrics and Gynecology
Luc Dirix, Helen Swaisland, Henk M W Verheul, Sylvie Rottey, Karin Leunen, Guy Jerusalem, Christian Rolfo, Dorte Nielsen, L Rhoda Molife, Rebecca Kristeleit, Judith de Vos-Geelen, Morten Mau-Sørensen, Patricia Soetekouw, Carla van Herpen, Anitra Fielding, Karen So, Wendy Bannister, Ruth Plummer
PURPOSE: The metabolism of olaparib, a potent inhibitor of poly(ADP-ribose) polymerase (PARP) with demonstrated efficacy in patients with BRCA-mutated ovarian cancer, is mediated by cytochrome P450 (CYP) enzymes (predominantly CYP3A4/5). We assessed the potential of a CYP3A4 inhibitor (itraconazole) and inducer (rifampin) to alter the pharmacokinetic (PK) profile of olaparib following single oral tablet doses. METHODS: Two Phase I, open-label, non-randomized trials were conducted in patients with advanced solid tumors...
October 10, 2016: Clinical Therapeutics
Olga Villamar Cruz, Tatiana Y Prudnikova, Daniela Araiza-Olivera, Carlos Perez-Plasencia, Neil Johnson, Andrea J Bernhardy, Michael Slifker, Catherine Renner, Jonathan Chernoff, Luis E Arias-Romero
Cells that are deficient in homologous recombination, such as those that have mutations in any of the Fanconi Anemia (FA)/BRCA genes, are hypersensitive to inhibition of poly(ADP-ribose) polymerase (PARP). However, FA/BRCA-deficient tumors represent a small fraction of breast cancers, which might restrict the therapeutic utility of PARP inhibitor monotherapy. The gene encoding the serine-threonine protein kinase p21-activated kinase 1 (PAK1) is amplified and/or overexpressed in several human cancer types including 25-30% of breast tumors...
October 11, 2016: Oncotarget
Ruth Heisey, June C Carroll
OBJECTIVE: To summarize the best evidence on strategies to identify and manage women with a family history of breast cancer. SOURCES OF INFORMATION: A PubMed search was conducted using the search terms breast cancer, guidelines, risk, family history, management, and magnetic resonance imaging screening from 2000 to 2016. Most evidence is level II. MAIN MESSAGE: Taking a good family history is essential when assessing breast cancer risk in order to identify women suitable for referral to a genetic counselor for possible genetic testing...
October 2016: Canadian Family Physician Médecin de Famille Canadien
Mansoor R Mirza, Bradley J Monk, Jørn Herrstedt, Amit M Oza, Sven Mahner, Andrés Redondo, Michel Fabbro, Jonathan A Ledermann, Domenica Lorusso, Ignace Vergote, Noa E Ben-Baruch, Christian Marth, Radosław Mądry, René D Christensen, Jonathan S Berek, Anne Dørum, Anna V Tinker, Andreas du Bois, Antonio González-Martín, Philippe Follana, Benedict Benigno, Per Rosenberg, Lucy Gilbert, Bobbie J Rimel, Joseph Buscema, John P Balser, Shefali Agarwal, Ursula A Matulonis
Background Niraparib is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer. We sought to evaluate the efficacy of niraparib versus placebo as maintenance treatment for patients with platinum-sensitive, recurrent ovarian cancer. Methods In this randomized, double-blind, phase 3 trial, patients were categorized according to the presence or absence of a germline BRCA mutation (gBRCA cohort and non-gBRCA cohort) and the type of non-gBRCA mutation and were randomly assigned in a 2:1 ratio to receive niraparib (300 mg) or placebo once daily...
October 7, 2016: New England Journal of Medicine
Bradley J Monk, Domenica Lorusso, Antoine Italiano, Stan B Kaye, Miguel Aracil, Adnan Tanović, Maurizio D'Incalci
Trabectedin is a marine-derived product that was originally isolated from the Caribbean sea squirt Ecteinascidia turbinata and the first anticancer marine drug to be approved by the European Union. It is currently used as a single agent for the treatment of patients with soft tissue sarcoma after failure of anthracyclines and ifosfamide, or for those patients who are unsuited to receive these agents, and in patients with relapsed, platinum-sensitive ovarian cancer in combination with pegylated liposomal doxorubicin...
September 15, 2016: Cancer Treatment Reviews
Kari Nyheim Solbrække, Håvard Søiland, Kirsten Lode, Birgitta Haga Gripsrud
In this paper we explore the rise of 'the breast cancer gene' as a field of medical, cultural and personal knowledge. We address its significance in the Norwegian public health care system in relation to so-called biological citizenship in this particular national context. One of our main findings is that, despite its claims as a measure for health and disease prevention, gaining access to medical knowledge of BRCA 1/2 breast cancer gene mutations can also produce severe instability in the individuals and families affected...
October 5, 2016: Medicine, Health Care, and Philosophy
Matteo Ghilli, Donatella M Mariniello, Giovanni Fanelli, Francesca Cascione, Andrea Fontana, Agostino Cristaudo, Anna Cilotti, Adelaide M Caligo, Giampiero Manca, Livio Colizzi, Antonio G Naccarato, Manuela Roncella
No abstract text is available yet for this article.
August 30, 2016: Clinical Breast Cancer
John S Kennedy, Patrick A Robbins
Breast MRI is being used more frequently for advanced screening for breast cancer. Patients may be at increased risk, or are symptomatic, with nonsuspicious mammograms. There is little data regarding the likelihood of a recommendation for biopsy, or for detecting a malignancy, in this population. We intended to determine the malignancy rate, number needed to treat, and positive predictive value for patients receiving adjunctive MRI at our institution. A retrospective review of all breast MRIs from 2008 to 2010 was done...
September 2016: American Surgeon
Jung-Min Lee, Cody J Peer, Minshu Yu, Lauren Amable, Nicolas Gordon, Christina M Annunziata, Nicole Houston, Andrew K L Goey, Tristan M Sissung, Bernard Parker, Lori Minasian, Victoria Chiou, Robert F Murphy, Brigitte C Widemann, William D Figg, Elise C Kohn
PURPOSE: Our preclinical studies showed the PARP inhibitor, olaparib prior to carboplatin attenuated carboplatin cytotoxicity. We evaluated sequence-specific pharmacokinetic/pharmacodynamic (PK/PD) effects, safety and activity of the combination. PATIENTS AND METHODS: Eligible patients had metastatic or recurrent women's cancer. Olaparib tablets were introduced (100 or 200mg bid, days1-7) in a 3+3 dose escalation with carboplatin AUC4 or 5 q21 days, up to eight cycles, followed by olaparib maintenance...
September 23, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Yaning Zhu, Jian Wu, Chengwan Zhang, Suan Sun, Jian Zhang, Wenjie Liu, Jian Huang, Zhihong Zhang
BRCA mutations occur frequently in breast cancer (BC), but their prognostic impact on outcomes of BC has not been determined. We conducted an updated meta-analysis on the association between BRCA mutations and survival in patients with BC. Electronic databases were searched. The primary outcome measure was overall survival (OS), and the secondary outcome measures included breast cancer-specific survival (BCSS) and event-free survival (EFS). Hazard ratios (HR) and 95% confidence interval (CI) were abstracted and pooled with random-effect modeling...
September 21, 2016: Oncotarget
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