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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.

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  • Authors+Show Affiliations

    ,

    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld TP4, Heidelberg, 69120, Germany. r.kaaks@dkfz.de.

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    Source

    Breast cancer research : BCR 14:3 2012 May 14 pg R76

    MeSH

    Adiposity
    Adult
    Age Factors
    Aged
    Aged, 80 and over
    Body Mass Index
    Breast Neoplasms
    Cohort Studies
    Estrogen Replacement Therapy
    Female
    Humans
    Middle Aged
    Postmenopause
    Premenopause
    Prospective Studies
    Receptors, Estrogen
    Receptors, Progesterone
    Risk
    Risk Factors
    Young Adult

    Pub Type(s)

    Journal Article
    Multicenter Study
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22583394

    Citation

    Ritte, Rebecca, 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 : BCR, vol. 14, no. 3, 2012, pp. R76.
    Ritte R, Lukanova A, Berrino F, et al. Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study. Breast Cancer Res. 2012;14(3):R76.
    Ritte, R., Lukanova, A., Berrino, F., Dossus, L., Tjønneland, A., Olsen, A., ... Kaaks, R. (2012). Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study. Breast Cancer Research : BCR, 14(3), pp. R76.
    Ritte R, et al. Adiposity, Hormone Replacement Therapy Use and Breast Cancer Risk By Age and Hormone Receptor Status: a Large Prospective Cohort Study. Breast Cancer Res. 2012 May 14;14(3):R76. PubMed PMID: 22583394.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: 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 Filskov, 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 Ramón, 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 Hm, AU - Krum-Hansen,Sanda, AU - Gram,Inger Torhild, 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, Y1 - 2012/05/14/ PY - 2011/12/20/received PY - 2012/03/12/revised PY - 2012/05/14/accepted PY - 2012/5/16/entrez PY - 2012/5/16/pubmed PY - 2013/3/12/medline SP - R76 EP - R76 JF - Breast cancer research : BCR JO - Breast Cancer Res. VL - 14 IS - 3 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. SN - 1465-542X UR - https://www.unboundmedicine.com/medline/citation/22583394/Adiposity_hormone_replacement_therapy_use_and_breast_cancer_risk_by_age_and_hormone_receptor_status:_a_large_prospective_cohort_study_ L2 - https://breast-cancer-research.biomedcentral.com/articles/10.1186/bcr3186 DB - PRIME DP - Unbound Medicine ER -