Research article
Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study
1 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld TP4, Heidelberg, 69120, Germany
2 Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, Milan, 20133, Italy
3 Institute of Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, Copenhagen, 2100, Denmark
4 Department of Cardiology, Aalborg Hospital, Aarhus University Hospital, Hobrovej 18-22, Aalborg, 9100, Denmark
5 Department of Epidemiology, School of Public Health, Aarhus University, Bartholins Allé 2, Aarhus, 8000, Denmark
6 Centre for Research in Epidemiology and Population Health, INSERM, Institut Gustave Roussy, 39 rue Camille Desmoulins, Villejuif, F-94805, France
7 Paris South University, UMRS 1018, Villejuif, F-94805, France
8 Division of Cancer Epidemiology and Prevention, Institute of Social and Preventive Medicine, Hirschengraben 84, Zurich, CH-8001, Switzerland
9 Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, Nuthetal, 14558, Germany
10 WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Asias Street 75 M., Goudi, Athens, GR-115 27, Greece
11 Hellenic Health Foundation, Tetrapoleos Street 10-12, Athens, GR-115 27, Greece
12 Department of Epidemiology, Harvard School of Public Health, Huntington Avenue 677, Boston, MA 02115, USA
13 Bureau of Epidemiologic Research, Academy of Athens, Panepistimiou Street 28, Athens, GR-106 79, Greece
14 Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Scientific Institute of Tuscany, Via Cosimo il Vecchio 2, Florence, 50139, Italy
15 Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian1, Milano, 20133, Italy
16 Department of Clinical and Experimental Medicine Medical School Federico II University Via S. Pansini 5 Naples, 80131, Italy
17 Cancer Registry and Histopathology Unit, 'Civile M.P. Arezzo' Hospital ASP 7, Via Dante 109, Ragusa, 97100, Italy
18 Centre for Environment and Health School of Public Health, Imperial College London, South Kensington Campus, London SW7 2AZ, UK
19 Human Genetics Foundation (HuGeF), Via Nizza 52, Torino,10126, Italy
20 Public Health and Health Planning Directorate, C/Ciriaco Miguel Virgil 9, Asturias, CP 33006, Spain
21 Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Avda Gran Via 199-203, Barcelona, 08907, Spain
22 Andalusian School of Public Health, Cuesta del Observatorio 4, Granada, E-1801, Spain
23 CIBER de Epidemiología y Salud Pública (CIBERESP), C/Melchor Fernández Almagro 3-5, Madrid, 28029, Spain
24 Public Health Division of Gipuzkoa, Institute BIO Donostia, Health Department, Basque Region, Avda de Navarra 4, Gipuzkoa, 20013, Spain
25 Department of Epidemiology, Murcia Regional Health Authority, Ronda de Levante 11, Murcia, 30008, Spain
26 Navarra Public Health Institute, Leyre 15, Pamplona, 31003, Spain
27 Department of Surgery and Perioperative Sciences, Umeå University Hospital, Building 10:1 Umeå, SE-901 85, Sweden
28 Department of Oncology and Radiation Sciences, Oncology, Umeå University Hospital, Building 6M, Umeå, SE-901 87, Sweden
29 National Institute for Public Health and the Environment, Antonie van Leeuwenhoeklaan 9, Bilthoven, 3721 MA, The Netherlands
30 Department of Gastroenterology and Hepatology, University Medical Centre, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands
31 Julius Center for Health Sciences and Primary Care, University Medical Center, Heidelberglaan 100, Utrecht, 3508 GA, The Netherlands
32 Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College, London, South Kensington Campus, London SW7 2AZ, UK
33 Institute of Community Medicine, University of Tromsø, MH Building, Tromsø, 9037, Norway
34 School of Clinical Medicine, University of Cambridge, The Old Schools, Trinity Lane, CB2 1TN, UK
35 Medical Research Council, Epidemiology Unit, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, UK
36 Cancer Epidemiology Unit, University of Oxford, Richard Doll Building, Oxford, OX3 7LF, UK
37 Nutritional Epidemiology Group, Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, Lyon, 69372, France
38 Department of Genomics of Common Disease, School of Public Health, Imperial College London, South Kensington Campus, London SW7 2AZ, UK
Breast Cancer Research 2012, 14:R76 doi:10.1186/bcr3186
Published: 14 May 2012Abstract
Introduction
Associations of hormone-receptor positive breast cancer with excess adiposity are reasonably well characterized; however, uncertainty remains regarding the association of body mass index (BMI) with hormone-receptor negative malignancies, and possible interactions by hormone replacement therapy (HRT) use.
Methods
Within the European EPIC cohort, Cox proportional hazards models were used to describe the relationship of BMI, waist and hip circumferences with risk of estrogen-receptor (ER) negative and progesterone-receptor (PR) negative (n = 1,021) and ER+PR+ (n = 3,586) breast tumors within five-year age bands. Among postmenopausal women, the joint effects of BMI and HRT use were analyzed.
Results
For risk of ER-PR- tumors, there was no association of BMI across the age bands. However, when analyses were restricted to postmenopausal HRT never users, a positive risk association with BMI (third versus first tertile HR = 1.47 (1.01 to 2.15)) was observed. BMI was inversely associated with ER+PR+ tumors among women aged ≤49 years (per 5 kg/m2 increase, HR = 0.79 (95%CI 0.68 to 0.91)), and positively associated with risk among women ≥65 years (HR = 1.25 (1.16 to 1.34)). Adjusting for BMI, waist and hip circumferences showed no further associations with risks of breast cancer subtypes. Current use of HRT was significantly associated with an increased risk of receptor-negative (HRT current use compared to HRT never use HR: 1.30 (1.05 to 1.62)) and positive tumors (HR: 1.74 (1.56 to 1.95)), although this risk increase was weaker for ER-PR- disease (Phet = 0.035). The association of HRT was significantly stronger in the leaner women (BMI ≤22.5 kg/m2) than for more overweight women (BMI ≥25.9 kg/m2) for, both, ER-PR- (HR: 1.74 (1.15 to 2.63)) and ER+PR+ (HR: 2.33 (1.84 to 2.92)) breast cancer and was not restricted to any particular HRT regime.
Conclusions
An elevated BMI may be positively associated with risk of ER-PR- tumors among postmenopausal women who never used HRT. Furthermore, postmenopausal HRT users were at an increased risk of ER-PR- as well as ER+PR+ tumors, especially among leaner women. For hormone-receptor positive tumors, but not for hormone-receptor negative tumors, our study confirms an inverse association of risk with BMI among young women of premenopausal age. Our data provide evidence for a possible role of sex hormones in the etiology of hormone-receptor negative tumors.
