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Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study.

Rebecca Ritte 1 Annekatrin Lukanova 1 Franco Berrino 2 Laure Dossus 1 Anne Tjønneland 3 Anja Olsen 3 Thure Filskov Overvad 4 Kim Overvad 5 Françoise Clavel-Chapelon 6 Agnès Fournier 6 Guy Fagherazzi 6 Sabine Rohrmann 1, 7 Birgit Teucher 1 Heiner Boeing 8 Krasimira Aleksandrova 8 Antonia Trichopoulou 9, 10 Pagona Lagiou 10 Dimitrios Trichopoulos 11, 12 Domenico Palli 13 Sabina Sieri 14 Salvatore Panico 15 Rosario Tumino 16 Paolo Vineis 17, 18 José Ramón Quirós 19 Genevieve Buckland 20 Maria-José Sánchez 21, 22 Pilar Amiano 23, 22 María-Dolores Chirlaque 22, 24 Eva Ardanaz 22, 25 Malin Sund 26 Per Lenner 27 Bas Bueno-De-Mesquita 28, 29 Carla van Gils 30 Petra Peeters 30, 31 Sanda Krum-Hansen 32 Inger Torhild Gram 32 Eiliv Lund 32 Kay-Tee Khaw 33 Nick Wareham 34 Naomi Allen 35 Timothy Key 35 Isabelle Romieu 36 Sabina Rinaldi 36 Afshan Siddiq 31, 37 David Cox 31 Elio Riboli 17 Rudolf Kaaks 1, * 
* Corresponding author
Abstract : ABSTRACT: 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)-progesterone receptor (PR)- (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 (3rd versus 1st tertile HR=1.47[1.01-2.15]) was observed. BMI was inversely associated with ER+PR+ tumors among women aged [less than or equal to]49 years (per 5kg/m2 increase, HR=0.79[95%CI 0.68-0.91]), and positively associated with risk among women [greater than or equal to]65 years (HR=1.25[1.16-1.34]). 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[1.05-1.62]) and positive tumors (HR: 1.74[1.56-1.95]), 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 [less than or equal to]22.5kg/m2) than for more overweight women (BMI [greater than or equal to]25.9kg/m2) for, both, ER-PR- (HR: 1.74[1.15-2.63]) and ER+PR+ (HR: 2.33[1.84-2.92]) 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 HR-positive tumors, but not for HR-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 HR-negative tumors.
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Submitted on : Monday, June 4, 2012 - 5:06:26 PM
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Rebecca Ritte, Annekatrin Lukanova, Franco Berrino, Laure Dossus, Anne Tjønneland, et al.. Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study.. Breast Cancer Research, BioMed Central, 2012, 14 (3), pp.R76. ⟨10.1186/bcr3186⟩. ⟨inserm-00704067⟩



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