title: A Prospective Evaluation of Early Detection Biomarkers for Ovarian Cancer in the European EPIC Cohort.
abstract: OBJECTIVE
  About 60% of ovarian cancers are diagnosed at late stage, when 5-year survival is less than 30% in contrast to 90% for local disease. This has prompted search for early detection biomarkers. For initial testing, specimens taken months or years before ovarian cancer diagnosis are the best source of information to evaluate early detection biomarkers. Here we evaluate the most promising ovarian cancer screening biomarkers in prospectively collected samples from the European Prospective Investigation into Cancer and Nutrition study.
  
  
  METHODS
  We measured CA125, HE4, CA72.4, and CA15.3 in 810 invasive epithelial ovarian cancer cases and 1,939 controls. We calculated the sensitivity at 95% and 98% specificity as well as area under the receiver operator curve (C-statistic) for each marker individually and in combination. In addition, we evaluated marker performance by stage at diagnosis and time between blood draw and diagnosis.
  
  
  RESULTS
  We observed the best discrimination between cases and controls within 6 months of diagnosis for CA125 (C-statistic = 0.92), then HE4 (0.84), CA72.4 (0.77), and CA15.3 (0.73). Marker performance declined with longer time between blood draw and diagnosis and for earlier staged disease. However, assessment of discriminatory ability at early stage was limited by small numbers. Combinations of markers performed modestly, but significantly better than any single marker.
  
  
  CONCLUSIONS
  CA125 remains the single best marker for the early detection of invasive epithelial ovarian cancer, but can be slightly improved by combining with other markers. Identifying novel markers for ovarian cancer will require studies including larger numbers of early-stage cases. Clin Cancer Res; 22(18); 4664-75. ©2016 AACRSee related commentary by Skates, p. 4542.
authors.affiliation: Ob/Gyn Epidemiology Center, Brigham and Women's Hospital, Boston, Massachusetts. Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, Massachusetts. r.kaaks@dkfz-heidelberg.de kterry@partners.org.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Terry
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Helena
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authors.lastname: Schock
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Renée T
authors.initials: RT
authors.lastname: Fortner
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Anika
authors.initials: A
authors.lastname: Hüsing
authors.affiliation: Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, Massachusetts. Genital Tract Biology Laboratory, Brigham and Women's Hospital, Boston, Massachusetts.
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authors.initials: RN
authors.lastname: Fichorova
authors.affiliation: Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, Massachusetts. Genital Tract Biology Laboratory, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Hidemi S
authors.initials: HS
authors.lastname: Yamamoto
authors.affiliation: Ob/Gyn Epidemiology Center, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Allison F
authors.initials: AF
authors.lastname: Vitonis
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Theron
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authors.lastname: Johnson
authors.affiliation: Department of Epidemiology, Aarhus University, Aarhus, Denmark.
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authors.affiliation: Danish Cancer Society Research Center, Copenhagen, Denmark.
authors.forename: Anne
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authors.affiliation: Université Paris-Sud, Centre de recherche en Épidémiologie et Santé des Populations (CESP), Institut Nationale de Santë et de Recherche Médicale (INSERM), Villejuif, France. Gustave Roussy, Villejuif, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Boutron-Ruault
authors.affiliation: Université Paris-Sud, Centre de recherche en Épidémiologie et Santé des Populations (CESP), Institut Nationale de Santë et de Recherche Médicale (INSERM), Villejuif, France. Gustave Roussy, Villejuif, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Mesrine
authors.affiliation: Université Paris-Sud, Centre de recherche en Épidémiologie et Santé des Populations (CESP), Institut Nationale de Santë et de Recherche Médicale (INSERM), Villejuif, France. Gustave Roussy, Villejuif, France. Human Genetics Foundation (HuGeF), Torino, Italy. Cancer Council Victoria and University of Melbourne, Australia.
authors.forename: Gianluca
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authors.affiliation: Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France.
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authors.affiliation: Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France.
authors.forename: Sabina
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authors.lastname: Rinaldi
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany.
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authors.affiliation: Helenic Health Foundation Athens, Athens, Greece. WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece.
authors.forename: Vassiliki
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authors.lastname: Benetou
authors.affiliation: Helenic Health Foundation Athens, Athens, Greece. WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece.
authors.forename: Pagona
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authors.lastname: Lagiou
authors.affiliation: Helenic Health Foundation Athens, Athens, Greece. WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece.
authors.forename: Antonia
authors.initials: A
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authors.affiliation: Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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authors.lastname: Krogh
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine and Laboratorio per le Tecnologie delle Terapie Avanzate (LTTA) Centre, University of Ferrara, Ferrara, Italy.
authors.forename: Elisabetta
authors.initials: E
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authors.affiliation: Dipartimento di Medicina Clinical e Chirurgia, Federico II University, Naples, Italy.
authors.forename: Salvatore
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authors.affiliation: National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
authors.forename: H Bas
authors.initials: HB
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authors.affiliation: Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: N Charlotte
authors.initials: NC
authors.lastname: Onland-Moret
authors.affiliation: Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Petra H
authors.initials: PH
authors.lastname: Peeters
authors.affiliation: Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
authors.forename: Inger Torhild
authors.initials: IT
authors.lastname: Gram
authors.affiliation: Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. Department of Research, Cancer Registry of Norway, Institute of Population-Based Case Research, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden. Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland.
authors.forename: Elisabete
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authors.affiliation: Unit of Nutrition and Cancer Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute, Catalan Institute of Oncology, Barcelona, Spain.
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authors.affiliation: Escuela Andaluza de Salud Publica, Instituto de Investigación Bionsanitaria ibs. Granada, Hospitales Universitarios de Granada, Granada, Spain. Centro de Investigación Biomédica En Red (CIBER), Section Epidemiology and Public Health (CIBERESP), Madrid, Spain.
authors.forename: Maria-Jose
authors.initials: MJ
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authors.affiliation: Centro de Investigación Biomédica En Red (CIBER), Section Epidemiology and Public Health (CIBERESP), Madrid, Spain. Navarra Public Health Institute, Pamplona, Spain. IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
authors.forename: Eva
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authors.lastname: Ardanaz
authors.affiliation: Centro de Investigación Biomédica En Red (CIBER), Section Epidemiology and Public Health (CIBERESP), Madrid, Spain. Public Health Division of Gipuzkoa, Regional Government of the Basque Country, Basque, Spain.
authors.forename: Nerea
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authors.affiliation: Centro de Investigación Biomédica En Red (CIBER), Section Epidemiology and Public Health (CIBERESP), Madrid, Spain. Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain.
authors.forename: Carmen
authors.initials: C
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authors.affiliation: Department of Clinical Sciences, Obstetrics and Gynecology Umeå, University of Umeå, Umeå, Sweden.
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authors.affiliation: Department of Medical Biosciences, Pathology Umeå, University of Umeå, Umeå, Sweden.
authors.forename: Eva
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authors.affiliation: Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Lund, Sweden. Department of Surgery, Skåne University Hospital, Lund University, Malmö, Sweden.
authors.forename: Karin
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authors.affiliation: Medical Research Council (MRC) Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.
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authors.affiliation: Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
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authors.affiliation: Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
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authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College of London, London, United Kingdom.
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authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College of London, London, United Kingdom.
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authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College of London, London, United Kingdom.
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authors.affiliation: Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, Massachusetts. r.kaaks@dkfz-heidelberg.de kterry@partners.org.
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mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D016022:Case-Control Studies; D015331:Cohort Studies; D055088:Early Detection of Cancer / Q000379:methods; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000453:epidemiology; D011446:Prospective Studies; D012372:ROC Curve; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor