title: Added Value of Serum Hormone Measurements in Risk Prediction Models for Breast Cancer for Women Not Using Exogenous Hormones: Results from the EPIC Cohort.
abstract: Purpose:Circulating hormone concentrations are associated with breast cancer risk, with well-established associations for postmenopausal women. Biomarkers may represent minimally invasive measures to improve risk prediction models.Experimental Design:We evaluated improvements in discrimination gained by adding serum biomarker concentrations to risk estimates derived from risk prediction models developed by Gail and colleagues and Pfeiffer and colleagues using a nested case-control study within the EPIC cohort, including 1,217 breast cancer cases and 1,976 matched controls. Participants were pre- or postmenopausal at blood collection. Circulating sex steroids, prolactin, insulin-like growth factor (IGF) I, IGF-binding protein 3, and sex hormone-binding globulin (SHBG) were evaluated using backward elimination separately in women pre- and postmenopausal at blood collection. Improvement in discrimination was evaluated as the change in concordance statistic (C-statistic) from a modified Gail or Pfeiffer risk score alone versus models, including the biomarkers and risk score. Internal validation with bootstrapping (1,000-fold) was used to adjust for overfitting.Results:Among women postmenopausal at blood collection, estradiol, testosterone, and SHBG were selected into the prediction models. For breast cancer overall, model discrimination after including biomarkers was 5.3 percentage points higher than the modified Gail model alone, and 3.4 percentage points higher than the Pfeiffer model alone, after accounting for overfitting. Discrimination was more markedly improved for estrogen receptor-positive disease (percentage point change in C-statistic: 7.2, Gail; 4.8, Pfeiffer). We observed no improvement in discrimination among women premenopausal at blood collection.Conclusions:Integration of hormone measurements in clinical risk prediction models may represent a strategy to improve breast cancer risk stratification.Clin Cancer Res; 23(15); 4181-9. ©2017 AACR.
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Anika
authors.initials: A
authors.lastname: Hüsing
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. r.fortner@dkfz-heidelberg.de.
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: Tilman
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authors.lastname: Kühn
authors.affiliation: Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark.
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.affiliation: Unit of Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark.
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.affiliation: Unit of Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark.
authors.forename: Anja
authors.initials: A
authors.lastname: Olsen
authors.affiliation: INSERM, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health team, Villejuif, France.|Université Paris Sud, UMRS 1018, Villejuif, France.|Gustave Roussy, Villejuif, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Boutron-Ruault
authors.affiliation: INSERM, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health team, Villejuif, France.|Université Paris Sud, UMRS 1018, Villejuif, France.|Gustave Roussy, Villejuif, France.|Human Genetics Foundation (HuGeF), Turin, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Severi
authors.affiliation: INSERM, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health team, Villejuif, France.|Université Paris Sud, UMRS 1018, Villejuif, France.|Gustave Roussy, Villejuif, France.
authors.forename: Agnes
authors.initials: A
authors.lastname: Fournier
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.affiliation: Hellenic Health Foundation, Athens, Greece.|WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, School of Medicine, Department of Hygiene, Epidemiology and Medical Statistics, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.affiliation: Hellenic Health Foundation, Athens, Greece.|WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, School of Medicine, Department of Hygiene, Epidemiology and Medical Statistics, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Benetou
authors.affiliation: Hellenic Health Foundation, Athens, Greece.|WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, School of Medicine, Department of Hygiene, Epidemiology and Medical Statistics, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Philippos
authors.initials: P
authors.lastname: Orfanos
authors.affiliation: Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Masala
authors.affiliation: Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Valeria
authors.initials: V
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authors.affiliation: Cancer Registry and Histopathology Unit, "Civic - M.P. Arezzo" Hospital, ASP Ragusa, Italy.
authors.forename: Rosario
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authors.affiliation: Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Fasanelli
authors.affiliation: Dipartimento di Medicina Clinica e Sperimentale, Federico II University, Naples, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Panico
authors.affiliation: Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.|Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom.
authors.forename: H Bas
authors.initials: HB
authors.lastname: Bueno de Mesquita
authors.affiliation: Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, the Netherlands.|MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom.
authors.forename: Petra H
authors.initials: PH
authors.lastname: Peeters
authors.affiliation: Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, the Netherlands.
authors.forename: Carla H
authors.initials: CH
authors.lastname: van Gills
authors.affiliation: Public Health Directorate, Asturias, Spain.
authors.forename: J Ramón
authors.initials: JR
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authors.affiliation: Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL. L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
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authors.affiliation: Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.Granada, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain.|CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
authors.forename: Maria-Jose
authors.initials: MJ
authors.lastname: Sánchez
authors.affiliation: CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.|Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia, Spain.|Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain.
authors.forename: Maria-Dolores
authors.initials: MD
authors.lastname: Chirlaque
authors.affiliation: CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.|Navarra Public Health Institute, Pamplona, Spain.|Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
authors.forename: Aurelio
authors.initials: A
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authors.affiliation: Public Health Division and Biodonostia Research Institute - Ciberesp, Basque Regional Health Department, San Sebastian, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Amiano
authors.affiliation: Cancer Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.affiliation: Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom.
authors.forename: Ruth C
authors.initials: RC
authors.lastname: Travis
authors.affiliation: Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Dossus
authors.affiliation: Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France.
authors.forename: Kuanrong
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authors.affiliation: Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France.
authors.forename: Pietro
authors.initials: P
authors.lastname: Ferrari
authors.affiliation: School of Public Health, Imperial College London, London, United Kingdom.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Merritt
authors.affiliation: School of Public Health, Imperial College London, London, United Kingdom.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Tzoulaki
authors.affiliation: School of Public Health, Imperial College London, London, United Kingdom.
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Rudolf
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mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000145:classification / Q000473:pathology; D016022:Case-Control Studies; D004958:Estradiol / Q000097:blood; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood; D017697:Premenopause / Q000097:blood; D011379:Prognosis; D011388:Prolactin / Q000097:blood; D012307:Risk Factors; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*; D013739:Testosterone / Q000097:blood
chemical_list: D014408:Biomarkers, Tumor; D012739:Gonadal Steroid Hormones; D018972:Insulin-Like Growth Factor Binding Protein 3; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D011388:Prolactin