title: Risk of second primary malignancies in women with breast cancer: Results from the European prospective investigation into cancer and nutrition (EPIC).
abstract: Women with a diagnosis of breast cancer are at increased risk of second primary cancers, and the identification of risk factors for the latter may have clinical implications. We have followed-up for 11 years 10,045 women with invasive breast cancer from a European cohort, and identified 492 second primary cancers, including 140 contralateral breast cancers. Expected and observed cases and Standardized Incidence Ratios (SIR) were estimated using Aalen-Johansen Markovian methods. Information on various risk factors was obtained from detailed questionnaires and anthropometric measurements. Cox proportional hazards regression models were used to estimate the role of risk factors. Women with breast cancer had a 30% excess risk for second malignancies (95% confidence interval-CI 18-42) after excluding contralateral breast cancers. Risk was particularly elevated for colorectal cancer (SIR, 1.71, 95% CI 1.43-2.00), lymphoma (SIR 1.80, 95% CI 1.31-2.40), melanoma (2.12; 1.63-2.70), endometrium (2.18; 1.75-2.70) and kidney cancers (2.40; 1.57-3.52). Risk of second malignancies was positively associated with age at first cancer, body mass index and smoking status, while it was inversely associated with education, post-menopausal status and a history of full-term pregnancy. We describe in a large cohort of women with breast cancer a 30% excess of second primaries. Among risk factors for breast cancer, a history of full-term pregnancy was inversely associated with the risk of second primary cancer.
authors: Unit of Cancer Epidemiology-CERMS, Department of Medical Sciences, University of Turin and Città Della Salute E Della Scienza Hospital, Turin, Italy.|Department of Mathematics "G. Peano", University of Turin, Turin, Italy.
authors: Fulvio
authors: F
authors: Ricceri
authors: Unit of Cancer Epidemiology-CERMS, Department of Medical Sciences, University of Turin and Città Della Salute E Della Scienza Hospital, Turin, Italy.
authors: Francesca
authors: F
authors: Fasanelli
authors: Department of Mathematics "G. Peano", University of Turin, Turin, Italy.
authors: Maria Teresa
authors: MT
authors: Giraudo
authors: Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, Italy.
authors: Sabina
authors: S
authors: Sieri
authors: Cancer Registry and Histopathology Unit, ", Civile M.P. Arezzo" Hospital, ASP, Ragusa, Italy.
authors: Rosario
authors: R
authors: Tumino
authors: Dipartimento Di Medicina Clinica E Chirurgia, Università Federico II, Napoli, Italy.
authors: Amalia
authors: A
authors: Mattiello
authors: Department of Public and Pediatric Health Sciences, University of Turin, Turin, Italy.
authors: Liliana
authors: L
authors: Vagliano
authors: Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute ISPO, Florence, Italy.
authors: Giovanna
authors: G
authors: Masala
authors: Public Health Directorate, Asturias, Spain.
authors: J Ramón
authors: JR
authors: Quirós
authors: Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Institut Catalá d'Oncologia, Barcelona, Spain.
authors: Noemie
authors: N
authors: Travier
authors: Andalusian School of Public Health, Granada Bio-Health Research Institute (Granada.IBS), Granada, Spain.|CIBER Epidemiología Y Salud Pública (CIBERESP), Spain.
authors: María-José
authors: MJ
authors: Sánchez
authors: Public Division of Gipuzkoa, Basque Regional Health Department and CIBERESP, San Sebastian, Spain.
authors: Nerea
authors: N
authors: Larranaga
authors: CIBER Epidemiología Y Salud Pública (CIBERESP), Spain.|Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain.
authors: María-Dolores
authors: MD
authors: Chirlaque
authors: CIBER Epidemiología Y Salud Pública (CIBERESP), Spain.|Navarra Public Health Institute, Pamplona, Spain.
authors: Eva
authors: E
authors: Ardanaz
authors: Danish Cancer Society Research Center, Copenhagen, Denmark.
authors: Anne
authors: A
authors: Tjonneland
authors: Danish Cancer Society Research Center, Copenhagen, Denmark.
authors: Anja
authors: A
authors: Olsen
authors: Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark.
authors: Kim
authors: K
authors: Overvad
authors: Unit of Genetic Epidemiology, Division of Cancer Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors: Jenny
authors: J
authors: Chang-Claude
authors: Unit of Genetic Epidemiology, Division of Cancer Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors: Rudolf
authors: R
authors: Kaaks
authors: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.
authors: Heiner
authors: H
authors: Boeing
authors: Inserm, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health Team, F, -94805, Villejuif, France.|University Paris Sud, UMRS 1018, F, -94805, Villejuif, France.|Institute Gustave Roussy, F, -94805, Villejuif, France.
authors: Françoise
authors: F
authors: Clavel-Chapelon
authors: Inserm, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health Team, F, -94805, Villejuif, France.|University Paris Sud, UMRS 1018, F, -94805, Villejuif, France.|Institute Gustave Roussy, F, -94805, Villejuif, France.
authors: Marina
authors: M
authors: Kvaskoff
authors: Inserm, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health Team, F, -94805, Villejuif, France.|University Paris Sud, UMRS 1018, F, -94805, Villejuif, France.|Institute Gustave Roussy, F, -94805, Villejuif, France.
authors: Laure
authors: L
authors: Dossus
authors: WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece.|Hellenic Health Foundation, Athens, Greece.
authors: Antonia
authors: A
authors: Trichopoulou
authors: WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece.
authors: Vassiliki
authors: V
authors: Benetou
authors: Hellenic Health Foundation, Athens, Greece.
authors: George
authors: G
authors: Adarakis
authors: National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.|Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands.|Department of Epidemiology and Biostatistics, the School of Public Health, Imperial College London, London, United Kingdom.|Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors: H B As
authors: HB
authors: Bueno-de-Mesquita
authors: Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands.
authors: Petra H
authors: PH
authors: Peeters
authors: Department of Surgical and Perioperative Sciences/Surgery, Umea University, Umea, Sweden.
authors: Malin
authors: M
authors: Sund
authors: Department of Radiation Sciences/Oncology, Umea University, Umea, Sweden.
authors: Anne
authors: A
authors: Andersson
authors: Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden.
authors: Signe
authors: S
authors: Borgquist
authors: Department of Surgery, Institute of Clinical Sciences, Skane University Hospital, Malmö, Sweden.
authors: Salma
authors: S
authors: Butt
authors: Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.|Department of Research, Cancer Registry of Norway, Oslo, Norway.|Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.|Department of Genetic Epidemiology, Folkhälsan Research Center, Helsinki, Finland.
authors: Elisabete
authors: E
authors: Weiderpass
authors: Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.
authors: Guri
authors: G
authors: Skeie
authors: Clinical Gerontology Unit, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors: Kay-Tee
authors: KT
authors: Khaw
authors: Cancer Epidemiology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors: Ruth C
authors: RC
authors: Travis
authors: International Agency for Research on Cancer (IARC), Lyon, France.
authors: Sabina
authors: S
authors: Rinaldi
authors: International Agency for Research on Cancer (IARC), Lyon, France.
authors: Isabelle
authors: I
authors: Romieu
authors: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
authors: Marc
authors: M
authors: Gunter
authors: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
authors: Mai
authors: M
authors: Kadi
authors: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
authors: Elio
authors: E
authors: Riboli
authors: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.|Unit of molecular and genetic epidemiology, Human Genetics Foundation (HuGeF), Turin, Italy.
authors: Paolo
authors: P
authors: Vineis
authors: Unit of Cancer Epidemiology-CERMS, Department of Medical Sciences, University of Turin and Città Della Salute E Della Scienza Hospital, Turin, Italy.
authors: Carlotta
authors: C
authors: Sacerdote
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000473:pathology*; D011247:Pregnancy; D016016:Proportional Hazards Models; D012307:Risk Factors
keywords: Aalen-Johansen estimator; breast cancer; second primary tumours; tumour size