TY - JOUR
T1 - Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status
T2 - A large prospective cohort study
AU - Ritte, Rebecca
AU - Lukanova, Annekatrin
AU - Berrino, Franco
AU - Dossus, Laure
AU - Tjønneland, Anne
AU - Olsen, Anja
AU - Overvad, Thure F.
AU - Overvad, Kim
AU - Clavel-Chapelon, Françoise
AU - Fournier, Agnès
AU - Fagherazzi, Guy
AU - Rohrmann, Sabine
AU - Teucher, Birgit
AU - Boeing, Heiner
AU - Aleksandrova, Krasimira
AU - Trichopoulou, Antonia
AU - Lagiou, Pagona
AU - Trichopoulos, Dimitrios
AU - Palli, Domenico
AU - Sieri, Sabina
AU - Panico, Salvatore
AU - Tumino, Rosario
AU - Vineis, Paolo
AU - Quirós, José R.
AU - Buckland, Genevieve
AU - Sánchez, Maria José
AU - Amiano, Pilar
AU - Chirlaque, María Dolores
AU - Ardanaz, Eva
AU - Sund, Malin
AU - Lenner, Per
AU - Bueno-de-Mesquita, Bas
AU - van Gils, Carla H.
AU - Peeters, Petra H.M.
AU - Krum-Hansen, Sanda
AU - Gram, Inger T.
AU - Lund, Eiliv
AU - Khaw, Kay Tee
AU - Wareham, Nick
AU - Allen, Naomi E.
AU - Key, Timothy J.
AU - Romieu, Isabelle
AU - Rinaldi, Sabina
AU - Siddiq, Afshan
AU - Cox, David
AU - Riboli, Elio
AU - Kaaks, Rudolf
N1 - Funding Information:
We would like to thank Jutta Schmitt and Jutta Kneisel for their assistance during the collection of hormone receptor status data, and we thank all the EPIC cohort participants for their contributions to data collection at baseline recruitment and during follow-up. Finally, the in-depth comments from the two anonymous reviewers are also greatly acknowledged. This work was (partly) supported by a grant from the German Research Foundation, Graduiertenkolleg 793: Epidemiology of communicable and chronic noncommunicable diseases and their interrelationships. The coordination of EPIC is financially supported by the European Commission Directorate General for Health and Consumer Protection (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark); Ligue contre le Cancer, Mutuelle Générale de l’Education Nationale, and the Institut National de la Santé et de la Recherche Médicale (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and the Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation, the Stavros Niarchos Foundation and the Hellenic Ministry of Health and Social Solidarity; the Italian Association for Research on Cancer (AIRC) and the National Research Council (Italy); the Dutch Ministry of Public Health, Welfare and Sport (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, the Nordic Centre of Excellence programme on Food, Nutrition and Health. (Norway); the Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (number 6236) and Navarra, and ISCIII RTICC Red Temática de Investigación Cooperativa en Cáncer (R06/0020) (Spain); the Swedish Cancer Society, Swedish Scientific Council and the Regional Government of Skåne and Västerbotten (Sweden); Cancer Research UK, and the Medical Research Council, (United Kingdom).
PY - 2012/5/14
Y1 - 2012/5/14
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84860813556
U2 - 10.1186/bcr3186
DO - 10.1186/bcr3186
M3 - Article
C2 - 22583394
AN - SCOPUS:84860813556
SN - 1465-5411
VL - 14
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 3
M1 - R76
ER -