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Journal Articles Nature Communications Year : 2023

Obesity-associated changes in molecular biology of primary breast cancer

1 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
2 University of British Columbia [Vancouver]
3 Lund University
4 Brigham and Women’s Hospital [Boston, MA]
5 CRUK - Cancer Research UK Cambridge Institute [Cambridge, Royaume-Uni]
6 UNIL - Université de Lausanne = University of Lausanne
7 Antoni van Leeuwenhoek Hospital
8 UON - University of Nottingham, UK
9 University of Iceland [Reykjavik]
10 UiB - University of Bergen
11 The University of Texas M.D. Anderson Cancer Center [Houston]
12 UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations] - The University of Queensland
13 Oslo University Hospital [Oslo]
14 Erasmus MC - Erasmus University Medical Center [Rotterdam]
15 University of Manitoba [Winnipeg]
16 CAM - University of Cambridge [UK]
17 Institut Jules Bordet [Bruxelles]
18 EORTC - European Organisation for Research and Treatment of Cancer [Bruxelles]
19 University of Dundee
20 Johns Hopkins University School of Medicine [Baltimore]
21 NKI - Netherlands Cancer Institute
22 Institut Curie [Paris]
23 Radboud University Medical Center [Nijmegen]
24 BCM - Baylor College of Medicine
25 UvA - University of Amsterdam [Amsterdam] = Universiteit van Amsterdam
26 UA - University of Antwerp
27 Helen Diller Family Comprehensive Cancer Center [San Francisco]
28 Synergie Lyon Cancer-Platform of Bioinformatics-Gilles Thomas
29 University Hospitals Leuven [Leuven]
30 UNIMI - Università degli Studi di Milano = University of Milan
Ake Borg
Annegien Broeks
  • Function : Author
Fatima Cardoso
Annuska M Glas
Andrew R Green
Hazem Khout
  • Function : Author
Stian Knappskog
Sunil R Lakhani
Amy E Mccart Reed
Serena Nik-Zainal
Martine Piccart
Colin Purdie
Anne Vincent-Salomon
Peter T Simpson
Marjanka K Schmidt
Christos Sotiriou
Kiat Tee Benita Tan
  • Function : Author
Stefania Tommasi
Giuseppe Viale
  • Function : Author
Hanne Vos
Anke T Witteveen
  • Function : Author
Giuseppe Floris
Ann Smeets

Abstract

Obesity is associated with an increased risk of developing breast cancer (BC) and worse prognosis in BC patients, yet its impact on BC biology remains understudied in humans. This study investigates how the biology of untreated primary BC differs according to patients’ body mass index (BMI) using data from >2,000 patients. We identify several genomic alterations that are differentially prevalent in overweight or obese patients compared to lean patients. We report evidence supporting an ageing accelerating effect of obesity at the genetic level. We show that BMI-associated differences in bulk transcriptomic profile are subtle, while single cell profiling allows detection of more pronounced changes in different cell compartments. These analyses further reveal an elevated and unresolved inflammation of the BC tumor microenvironment associated with obesity, with distinct characteristics contingent on the estrogen receptor status. Collectively, our analyses imply that obesity is associated with an inflammaging-like phenotype. We conclude that patient adiposity may play a significant role in the heterogeneity of BC and should be considered for BC treatment tailoring.
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Dates and versions

hal-04209701 , version 1 (18-09-2023)

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Ha-Linh Nguyen, Tatjana Geukens, Marion Maetens, Samuel Aparicio, Ayse Bassez, et al.. Obesity-associated changes in molecular biology of primary breast cancer. Nature Communications, 2023, 14, pp.4418. ⟨10.1038/s41467-023-39996-z⟩. ⟨hal-04209701⟩
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