Added value of serum hormone measurements in risk prediction models for breast cancer for women not using exogenous hormones: Results from the EPIC cohort

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  • Anika Hüsing, Division of Cancer Epidemiology, German Cancer Research Center (DKFZ)., Germany
  • Renée T Fortner, Division of Cancer Epidemiology, German Cancer Research Center (DKFZ) r.fortner@dkfz-heidelberg.de., Germany
  • Tilman Kühn, Division of Cancer Epidemiology, German Cancer Research Center (DKFZ)., Germany
  • Kim Overvad
  • Anne Tjonneland, Diet, Genes and Environment, Danish Cancer Society Research Centre, Denmark
  • Anja Olsen
  • Marie-Christine Boutron-Ruault, Université Paris-Saclay, Univ. Paris-Sud, UVSQ, Inserm, CESP, Generations and health., France
  • Gianluca Severi, HuGeF-Human Genetics Foundation, France
  • Agnes Fournier, Nutrition, Hormones and Women's Health Team, INSERM, CESP Centre for Research in Epidemiology and Population Health, U1018, Univ Paris Sud., France
  • Heiner Boeing, Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke., Germany
  • Antonia Trichopoulou, Bureau of Epidemiologic Research, Academy of Athens., Greece
  • Vassiliki Benetou, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece., Greece
  • Philippos Orfanos, Hellenic Health Foundation, Athens, Greece
  • Giovanna Masala, I S P O (Cancer Research and Prevention Institute), Molecular and Nutritional Epidemiology Unit., Italy
  • Valeria Pala, Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori., Italy
  • Rosario Tumino, Cancer Registry and Histopathology Unit, "Civic-M.P.Arezzo" Hospital, ASP, Via Dante N° 109, 97100 Ragusa, Italy., Italy
  • Francesca Fasanelli, Dipartimento di Scienze Mediche, Università di Torino., Italy
  • Salvatore Panico, Department of Clinical Medicine and Surgery, Section of Endocrinology, Federico II University., Italy
  • Bas H Bueno-De-Mesquita, National Institute for Public Health and the Environment (RIVM), Netherlands
  • Petra Peeters, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands., Netherlands
  • Carla H van Gils, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands., Netherlands
  • J Ramon Quiros, Public Health Directorate, Asturias, Spain., Spain
  • Antonio Agudo, Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), 08908 Barcelona, Spain., Spain
  • Maria-Jose Sánchez, Andalucian School of Public Health, Research Institute Biosanitary Granada., Grenada
  • María-Dolores Chirlaque, CIBER en Epidemiologia y Salud Publica (CIBERESP), Epidemiology Department, Murcia Health Council., Spain
  • Aurelio Barricarte, CIBER Epidemiologia y Salud Publica (CIBERESP)., Spain
  • Pilar Amiano, Public Health Division of Gipuzkoa, Basque Government, Spain; Health Research Institute, Biodonostia, San Sebastián, Spain., Spain
  • Kay-Tee Khaw, Clinical Gerontology Unit, School of Clinical Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Rd, Cambridge CB2 0SP, UK., United Kingdom
  • Ruth C. Travis, Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK., United Kingdom
  • Laure Dossus, IARC, France
  • Kuanrong Li, International Agency for Research on Cancer (IARC-WHO)., France
  • Pietro Ferrari, Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France., France
  • Melissa A Merritt, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom, United Kingdom
  • Ioanna Tzoulaki, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom, United Kingdom
  • Elio Riboli, School of Public Health, Imperial College London, London, UK., United Kingdom
  • Rudolf Kaaks, Division of Cancer Epidemiology, German Cancer Research Centre k.tikk@dkfz.de., Germany

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 et al. and Pfeiffer et al. using a nested case-control study within the EPIC cohort including 1217 breast cancer cases and 1976 matched controls. Participants were pre- or postmenopausal at blood collection. Circulating sex steroids, prolactin, insulin-like growth factor 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 C-statistic from a modified Gail or Pfeiffer risk score alone vs. models including the biomarkers and risk score. Internal validation with bootstrapping (1000-fold) was used to adjust for over-fitting.

RESULTS: Among women postmenopausal at blood collection, estradiol, testosterone and SHBG were selected into the prediction models. For breast cancer overall, discrimination 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 over-fitting. Discrimination was more markedly improved for estrogen receptor (ER)+ 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.

Original languageEnglish
JournalClinical Cancer Research
Volume23
Issue15
Pages (from-to)4181-4189
Number of pages9
ISSN1078-0432
DOIs
Publication statusPublished - 1 Aug 2017

    Research areas

  • Journal Article

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