Dataset Information

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

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.

SUBMITTER: Ritte R

PROVIDER: S-EPMC3446339 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Publications

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

Ritte Rebecca R Lukanova Annekatrin A Berrino Franco F Dossus Laure L Tjønneland Anne A Olsen Anja A Overvad Thure Filskov TF Overvad Kim K Clavel-Chapelon Françoise F Fournier Agnès A Fagherazzi Guy G Rohrmann Sabine S Teucher Birgit B Boeing Heiner H Aleksandrova Krasimira K Trichopoulou Antonia A Lagiou Pagona P Trichopoulos Dimitrios D Palli Domenico D Sieri Sabina S Panico Salvatore S Tumino Rosario R Vineis Paolo P Quirós José Ramón JR Buckland Genevieve G Sánchez Maria-José MJ Amiano Pilar P Chirlaque María-Dolores MD Ardanaz Eva E Sund Malin M Lenner Per P Bueno-de-Mesquita Bas B van Gils Carla H CH Peeters Petra Hm PH Krum-Hansen Sanda S Gram Inger Torhild IT Lund Eiliv E Khaw Kay-Tee KT Wareham Nick N Allen Naomi E NE Key Timothy J TJ Romieu Isabelle I Rinaldi Sabina S Siddiq Afshan A Cox David D Riboli Elio E Kaaks Rudolf R

Breast cancer research : BCR 20120514 3

<h4>Introduction</h4>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.<h4>Methods</h4>Within the European EPIC cohort, Cox proportional hazards models were used to describe the relationship of BMI, waist and hip circumferences with risk of estr ...[more]

PMID: 22583394

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Project description:BACKGROUND:Menopausal hormone therapy (MHT) increases breast cancer (BC) risk, but cohort studies largely consider use only at enrollment. Evidence is limited on how changes in MHT use alter the magnitude of risk, and whether risk varies between invasive and in situ cancer, by histology or by hormone receptor status. METHODS:We investigated the roles of estrogen-alone therapy (ET) and estrogen plus progestin therapy (EPT) on BC risk overall, by histology and estrogen receptor (ER) and progesterone receptor (PR) status, and on incidence of in situ disease, in the NIH-AARP cohort. Participants included 118,760 postmenopausal women (50-71?years), of whom 63.5% (n?=?75,398) provided MHT use information at baseline in 1996 and in a follow-up survey in 2004, subsequent to the dissemination in 2002 of the Women's Health Initiative trial safety concerns regarding EPT. ET analyses included 50,476 women with hysterectomy (31,439 with follow-up data); EPT analyses included 68,284 women with intact uteri (43,959 with follow-up data). Adjusted hazard ratios (HRs) were estimated using Cox proportional hazards models using age as the time metric with follow-up through 2011. RESULTS:Eight thousand three hundred thirty-three incident BC cases were accrued, 2479 in women with follow-up data. BC risk was not elevated in current ET users at baseline (HR?=?1.05, 95% confidence interval [CI] CI?=?0.95-1.16) but was higher in women continuing use through 2004 (HR?=?1.35, 95% CI?=?1.04-1.75). Ever EPT use at baseline was associated with elevated BC risk overall (HR?=?1.54 (1.44-1.64), with a doubling in risk for women with 10 or more years of use, for in situ disease, and across subtypes defined by histology and ER/PR status (all p?<?0.004). Risk persisted in women who continued EPT through 2004 (HR?=?1.80, 95% CI?=?1.39-2.32). In contrast, no association was seen in women who discontinued EPT before 2004 (HR?=?1.14, 95% CI?=?0.99-1.30). CONCLUSIONS:ET use was not associated with BC risk in this cohort, although excess risk was suggested in women who continued use through 2004. EPT use was linked to elevated in situ and invasive BC risk, and elevated risk across invasive BC histologic and hormone receptor-defined subtypes, with the highest risk for women who continued use through the 2004 follow-up survey.

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Dataset Information

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

Introduction

Methods

Results

Conclusions

Publications

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

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