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01-02-2019 | Epidemiology

Molecular mechanisms linking high body mass index to breast cancer etiology in post-menopausal breast tumor and tumor-adjacent tissues

Authors: Yujing J. Heng, Jun Wang, Thomas U. Ahearn, Susan B. Brown, Xuehong Zhang, Christine B. Ambrosone, Victor Piana de Andrade, Adam M. Brufsky, Fergus J. Couch, Tari A. King, Francesmary Modugno, Celine M. Vachon, Natalie C. DuPre, Montserrat Garcia-Closas, Melissa A. Troester, David J. Hunter, A. Heather Eliassen, Rulla M. Tamimi, Susan E. Hankinson, Andrew H. Beck

Published in: Breast Cancer Research and Treatment | Issue 3/2019

Abstract

Purpose

In post-menopausal women, high body mass index (BMI) is an established breast cancer risk factor and is associated with worse breast cancer prognosis. We assessed the associations between BMI and gene expression of both breast tumor and adjacent tissue in estrogen receptor-positive (ER+) and estrogen receptor-negative (ER−) diseases to help elucidate the mechanisms linking obesity with breast cancer biology in 519 post-menopausal women from the Nurses’ Health Study (NHS) and NHSII.

Methods

Differential gene expression was analyzed separately in ER+ and ER− disease both comparing overweight (BMI ≥ 25 to < 30) or obese (BMI ≥ 30) women to women with normal BMI (BMI < 25), and per 5 kg/m² increase in BMI. Analyses controlled for age and year of diagnosis, physical activity, alcohol consumption, and hormone therapy use. Gene set enrichment analyses were performed and validated among a subset of post-menopausal cases in The Cancer Genome Atlas (for tumor) and Polish Breast Cancer Study (for tumor-adjacent).

Results

No gene was differentially expressed by BMI (FDR < 0.05). BMI was significantly associated with increased cellular proliferation pathways, particularly in ER+ tumors, and increased inflammation pathways in ER− tumor and ER− tumor-adjacent tissues (FDR < 0.05). High BMI was associated with upregulation of genes involved in epithelial-mesenchymal transition in ER+ tumor-adjacent tissues.

Conclusions

This study provides insights into molecular mechanisms of BMI influencing post-menopausal breast cancer biology. Tumor and tumor-adjacent tissues provide independent information about potential mechanisms.

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Title: Molecular mechanisms linking high body mass index to breast cancer etiology in post-menopausal breast tumor and tumor-adjacent tissues
Authors: Yujing J. Heng
Jun Wang
Thomas U. Ahearn
Susan B. Brown
Xuehong Zhang
Christine B. Ambrosone
Victor Piana de Andrade
Adam M. Brufsky
Fergus J. Couch
Tari A. King
Francesmary Modugno
Celine M. Vachon
Natalie C. DuPre
Montserrat Garcia-Closas
Melissa A. Troester
David J. Hunter
A. Heather Eliassen
Rulla M. Tamimi
Susan E. Hankinson
Andrew H. Beck
Publication date: 01-02-2019
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 3/2019
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-018-5034-1

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