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BACKGROUND Olaparib, a novel, orally active poly(ADP-ribose) polymerase (PARP) inhibitor, induced synthetic lethality in BRCA-deficient cells. A maximum tolerated dose and initial signal of efficacy in BRCA-deficient ovarian cancers have been reported. We therefore assessed the efficacy, safety, and tolerability of olaparib alone in women with BRCA1 or(More)
PURPOSE The prognostic significance of germline BRCA1 and BRCA2 mutations in Jewish patients with pancreatic adenocarcinoma (PAC) is unknown. Our objective was to define the prevalence of BRCA1 and BRCA2 in an unselected group of Jewish patients and to compare the clinical characteristics and overall survival (OS) of patients with resected BRCA(More)
BACKGROUND Risk-reducing salpingo-oophorectomy is often considered by carriers of BRCA mutations who have completed childbearing. However, there are limited data supporting the efficacy of this approach. We prospectively compared the effect of risk-reducing salpingo-oophorectomy with that of surveillance for ovarian cancer on the incidence of subsequent(More)
BACKGROUND Previously, small studies have found that BRCA1 and BRCA2 breast tumors differ in their pathology. Analysis of larger datasets of mutation carriers should allow further tumor characterization. METHODS We used data from 4,325 BRCA1 and 2,568 BRCA2 mutation carriers to analyze the pathology of invasive breast, ovarian, and contralateral breast(More)
BACKGROUND The prognostic significance of germline mutations in BRCA1 and BRCA2 in women with breast cancer remains unclear. A combined analysis was performed to address this uncertainty. METHODS Two retrospective cohorts of Ashkenazi Jewish women undergoing breast-conserving treatment for invasive cancer between 1980 and 1995 (n = 584) were established.(More)
Anonymity is increasingly important for networked applications amidst concerns over censorship and privacy. In this paper, we describe Herbivore, a peer-to-peer, scalable, tamper-resilient communication system that provides provable anonymity and privacy. Building on dining cryptographer networks, Herbivore scales by partitioning the network into(More)
Anonymity is increasingly important for networked applications amidst concerns over censorship and privacy. This paper outlines the design of HerbivoreFS, a scalable and efficient file sharing system that provides strong anonymity. HerbivoreFS provides computational guarantees that even adversaries able to monitor all network traffic cannot deduce the(More)
The American Society of Clinical Oncology (ASCO) has long affirmed that the recognition and management of individuals with an inherited susceptibility to cancer are core elements of oncology care. ASCO released its first statement on genetic testing in 1996 and updated that statement in 2003 and 2010 in response to developments in the field. In 2014, the(More)
The underlying mechanism behind age-induced wastage of the human ovarian follicle reserve is unknown. We identify impaired ATM (ataxia-telangiectasia mutated)-mediated DNA double-strand break (DSB) repair as a cause of aging in mouse and human oocytes. We show that DSBs accumulate in primordial follicles with age. In parallel, expression of key DNA DSB(More)