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Germline mutation i...
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Candido-dos-Reis, Francisco JUniversity of São Paulo
(author)
Germline mutation in BRCA1 or BRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer
- Article/chapterEnglish2015
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LIBRIS-ID:oai:lup.lub.lu.se:8078080a-4b99-4821-86e6-524080ddf2fd
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https://lup.lub.lu.se/record/4816564URI
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https://doi.org/10.1158/1078-0432.CCR-14-2497DOI
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Language:English
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Summary in:English
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
Notes
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PURPOSE: To analyze the effect of germline mutations in BRCA1 and BRCA2 on mortality in patients with ovarian cancer up to 10 years after diagnosis.EXPERIMENTAL DESIGN: We used unpublished survival time data for 2,242 patients from two case-control studies and extended survival time data for 4,314 patients from previously reported studies. All participants had been screened for deleterious germline mutations in BRCA1 and BRCA2. Survival time was analyzed for the combined data using Cox proportional hazard models with BRCA1 and BRCA2 as time-varying covariates. Competing risks were analyzed using Fine and Gray model.RESULTS: The combined 10-year overall survival rate was 30% [95% confidence interval (CI), 28%-31%] for non-carriers, 25% (95% CI, 22%-28%) for BRCA1 carriers, and 35% (95% CI, 30%-41%) for BRCA2 carriers. The HR for BRCA1 was 0.53 at time zero and increased over time becoming greater than one at 4.8 years. For BRCA2, the HR was 0.42 at time zero and increased over time (predicted to become greater than 1 at 10.5 years). The results were similar when restricted to 3,202 patients with high-grade serous tumors and to ovarian cancer-specific mortality.CONCLUSIONS: BRCA1/2 mutations are associated with better short-term survival, but this advantage decreases over time and in BRCA1 carriers is eventually reversed. This may have important implications for therapy of both primary and relapsed disease and for analysis of long-term survival in clinical trials of new agents, particularly those that are effective in BRCA1/2 mutation carriers.
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Song, HonglinUniversity of Cambridge
(author)
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Goode, Ellen LMayo Clinic Minnesota
(author)
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Cunningham, Julie MMayo Clinic Minnesota
(author)
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Fridley, Brooke LUniversity of Kansas Medical Center
(author)
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Larson, Melissa CMayo Clinic Minnesota
(author)
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Alsop, KathrynPeter MacCallum Cancer Centre
(author)
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Dicks, EdUniversity of Cambridge
(author)
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Harrington, PatriciaUniversity of Cambridge
(author)
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Ramus, Susan JUniversity of Southern California
(author)
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de Fazio, AnnaUniversity of Sydney
(author)
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Mitchell, GillianPeter MacCallum Cancer Centre
(author)
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Fereday, SianPeter MacCallum Cancer Centre
(author)
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Bolton, Kelly LNational Cancer Institute, USA
(author)
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Gourley, CharlieUniversity of Edinburgh
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Michie, CarolineNinewells Hospital and Medical School
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Karlan, BethCedars-Sinai Medical Center
(author)
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Lester, JennyCedars-Sinai Medical Center
(author)
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Walsh, ChristineCedars-Sinai Medical Center
(author)
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Cass, IlanaCedars-Sinai Medical Center
(author)
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Olsson, HåkanLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)onk-hol
(author)
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Gore, MartinRoyal Marsden NHS Foundation Trust
(author)
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Benitez, Javier JSpanish National Cancer Research Center (CNIO)
(author)
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Garcia, Maria JSpanish National Cancer Research Center (CNIO)
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Andrulis, IreneUniversity of Toronto
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Mulligan, Anna MarieUniversity of Toronto
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Glendon, GordUniversity of Toronto
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Blanco, IgnacioCatalan Institute of Oncology
(author)
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Lazaro, ConxiCatalan Institute of Oncology
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Whittemore, Alice SStanford University
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McGuire, ValerieStanford University
(author)
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Sieh, WeivaStanford University
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Montagna, MarcoVeneto Institute of Oncology
(author)
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Alducci, ElisaVeneto Institute of Oncology
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Sadetzki, SiegalGertner Institute for Epidemiology and Health Policy Research
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Chetrit, AngelaGertner Institute for Epidemiology and Health Policy Research
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Kwong, AvaHong Kong Sanatorium & Hospital
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Kjaer, Susanne KDanish Cancer Society
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Jensen, AllanDanish Cancer Society
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Høgdall, EstridUniversity of Copenhagen
(author)
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Neuhausen, SusanBeckman Research Institute of City of Hope
(author)
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Nussbaum, RobertUniversity of California, San Francisco
(author)
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Daly, MaryFox Chase Cancer Center
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Greene, Mark HNational Cancer Institute, USA
(author)
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Mai, Phuong LNational Cancer Institute, USA
(author)
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Loud, Jennifer TNational Cancer Institute, USA
(author)
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Moysich, KirstenRoswell Park Cancer Institute
(author)
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Toland, Amanda EOhio State University
(author)
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Lambrechts, DietherCatholic University of Leuven
(author)
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Ellis, SteveUniversity of Cambridge
(author)
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University of São PauloUniversity of Cambridge
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In:Clinical Cancer Research21:3, s. 7-6521078-0432
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Candido-dos-Reis ...
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Song, Honglin
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Goode, Ellen L
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Cunningham, Juli ...
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Fridley, Brooke ...
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Larson, Melissa ...
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Alsop, Kathryn
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Dicks, Ed
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Ramus, Susan J
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de Fazio, Anna
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Fereday, Sian
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Bolton, Kelly L
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Gourley, Charlie
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Michie, Caroline
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Karlan, Beth
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Lester, Jenny
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Walsh, Christine
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Cass, Ilana
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Olsson, Håkan
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Gore, Martin
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Benitez, Javier ...
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Garcia, Maria J
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Andrulis, Irene
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Mulligan, Anna M ...
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Glendon, Gord
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Lazaro, Conxi
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Whittemore, Alic ...
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McGuire, Valerie
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Sieh, Weiva
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Montagna, Marco
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Alducci, Elisa
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Sadetzki, Siegal
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Chetrit, Angela
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Kwong, Ava
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Kjaer, Susanne K
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Jensen, Allan
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Høgdall, Estrid
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Neuhausen, Susan
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Nussbaum, Robert
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Daly, Mary
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Greene, Mark H
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Mai, Phuong L
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Loud, Jennifer T
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Lambrechts, Diet ...
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