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Int J Cancer. 2015 Aug 15;137(4):940-8. doi: 10.1002/ijc.29462. Epub 2015 Feb 13.

Risk of second primary malignancies in women with breast cancer: Results from the European prospective investigation into cancer and nutrition (EPIC).

Author information

1
Unit of Cancer Epidemiology-CERMS, Department of Medical Sciences, University of Turin and Città Della Salute E Della Scienza Hospital, Turin, Italy.
2
Department of Mathematics "G. Peano", University of Turin, Turin, Italy.
3
Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, Italy.
4
Cancer Registry and Histopathology Unit, ", Civile M.P. Arezzo" Hospital, ASP, Ragusa, Italy.
5
Dipartimento Di Medicina Clinica E Chirurgia, Università Federico II, Napoli, Italy.
6
Department of Public and Pediatric Health Sciences, University of Turin, Turin, Italy.
7
Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute ISPO, Florence, Italy.
8
Public Health Directorate, Asturias, Spain.
9
Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Institut Catalá d'Oncologia, Barcelona, Spain.
10
Andalusian School of Public Health, Granada Bio-Health Research Institute (Granada.IBS), Granada, Spain.
11
CIBER Epidemiología Y Salud Pública (CIBERESP), Spain.
12
Public Division of Gipuzkoa, Basque Regional Health Department and CIBERESP, San Sebastian, Spain.
13
Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain.
14
Navarra Public Health Institute, Pamplona, Spain.
15
Danish Cancer Society Research Center, Copenhagen, Denmark.
16
Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark.
17
Unit of Genetic Epidemiology, Division of Cancer Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
18
Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.
19
Inserm, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health Team, F, -94805, Villejuif, France.
20
University Paris Sud, UMRS 1018, F, -94805, Villejuif, France.
21
Institute Gustave Roussy, F, -94805, Villejuif, France.
22
WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece.
23
Hellenic Health Foundation, Athens, Greece.
24
National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
25
Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands.
26
Department of Epidemiology and Biostatistics, the School of Public Health, Imperial College London, London, United Kingdom.
27
Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
28
Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands.
29
Department of Surgical and Perioperative Sciences/Surgery, Umea University, Umea, Sweden.
30
Department of Radiation Sciences/Oncology, Umea University, Umea, Sweden.
31
Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden.
32
Department of Surgery, Institute of Clinical Sciences, Skane University Hospital, Malmö, Sweden.
33
Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.
34
Department of Research, Cancer Registry of Norway, Oslo, Norway.
35
Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
36
Department of Genetic Epidemiology, Folkhälsan Research Center, Helsinki, Finland.
37
Clinical Gerontology Unit, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom.
38
Cancer Epidemiology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
39
International Agency for Research on Cancer (IARC), Lyon, France.
40
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
41
Unit of molecular and genetic epidemiology, Human Genetics Foundation (HuGeF), Turin, Italy.

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.

KEYWORDS:

Aalen-Johansen estimator; breast cancer; second primary tumours; tumour size

PMID:
25650288
DOI:
10.1002/ijc.29462
[Indexed for MEDLINE]
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