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Breast Cancer Research
Published in: Breast Cancer Research 3/2012

Open Access 01-06-2012 | Research article

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

Authors: Rebecca Ritte, Annekatrin Lukanova, Franco Berrino, Laure Dossus, Anne Tjønneland, Anja Olsen, Thure Filskov Overvad, Kim Overvad, Françoise Clavel-Chapelon, Agnès Fournier, Guy Fagherazzi, Sabine Rohrmann, Birgit Teucher, Heiner Boeing, Krasimira Aleksandrova, Antonia Trichopoulou, Pagona Lagiou, Dimitrios Trichopoulos, Domenico Palli, Sabina Sieri, Salvatore Panico, Rosario Tumino, Paolo Vineis, José Ramón Quirós, Genevieve Buckland, Maria-José Sánchez, Pilar Amiano, María-Dolores Chirlaque, Eva Ardanaz, Malin Sund, Per Lenner, Bas Bueno-de-Mesquita, Carla H van Gils, Petra HM Peeters, Sanda Krum-Hansen, Inger Torhild Gram, Eiliv Lund, Kay-Tee Khaw, Nick Wareham, Naomi E Allen, Timothy J Key, Isabelle Romieu, Sabina Rinaldi, Afshan Siddiq, David Cox, Elio Riboli, Rudolf Kaaks

Published in: Breast Cancer Research | Issue 3/2012

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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) 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.
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Metadata
Title
Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study
Authors
Rebecca Ritte
Annekatrin Lukanova
Franco Berrino
Laure Dossus
Anne Tjønneland
Anja Olsen
Thure Filskov Overvad
Kim Overvad
Françoise Clavel-Chapelon
Agnès Fournier
Guy Fagherazzi
Sabine Rohrmann
Birgit Teucher
Heiner Boeing
Krasimira Aleksandrova
Antonia Trichopoulou
Pagona Lagiou
Dimitrios Trichopoulos
Domenico Palli
Sabina Sieri
Salvatore Panico
Rosario Tumino
Paolo Vineis
José Ramón Quirós
Genevieve Buckland
Maria-José Sánchez
Pilar Amiano
María-Dolores Chirlaque
Eva Ardanaz
Malin Sund
Per Lenner
Bas Bueno-de-Mesquita
Carla H van Gils
Petra HM Peeters
Sanda Krum-Hansen
Inger Torhild Gram
Eiliv Lund
Kay-Tee Khaw
Nick Wareham
Naomi E Allen
Timothy J Key
Isabelle Romieu
Sabina Rinaldi
Afshan Siddiq
David Cox
Elio Riboli
Rudolf Kaaks
Publication date
01-06-2012
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 3/2012
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr3186

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