Obesity-associated changes in molecular biology of primary breast cancer

Ha-Linh Nguyen (1) , Tatjana Geukens (1) , Marion Maetens (1) , Samuel Aparicio (2) , Ayse Bassez (1) , Ake Borg (3) , Jane Brock (4) , Annegien Broeks , Carlos Caldas (5) , Fatima Cardoso , Maxim de Schepper (1) , Mauro Delorenzi (6) , Caroline A Drukker (7) , Annuska M Glas , Andrew R Green (8) , Edoardo Isnaldi (1) , Jórunn Eyfjörð (9) , Hazem Khout , Stian Knappskog (10) , Savitri Krishnamurthy (11) , Sunil R Lakhani (12) , Anita Langerod (13) , John W M Martens (14) , Amy E Mccart Reed (12) , Leigh Murphy (15) , Stefan Naulaerts (1) , Serena Nik-Zainal (16) , Ines Nevelsteen (1) , Patrick Neven (1) , Martine Piccart (17) , Coralie Poncet (18) , Kevin Punie (1) , Colin Purdie (19) , Emad A Rakha (8) , Andrea Richardson (20) , Emiel Rutgers (21) , Anne Vincent-Salomon (22) , Peter T Simpson , Marjanka K Schmidt , Christos Sotiriou (17) , Paul N Span (23) , Kiat Tee Benita Tan , Alastair Thompson (24) , Stefania Tommasi , Karen van Baelen (1) , Marc van de Vijver (25) , Steven van Laere (26) , Laura Van’t Veer (27) , Giuseppe Viale , Alain Viari (28) , Hanne Vos (29) , Anke T Witteveen , Hans Wildiers (1) , Giuseppe Floris (29) , Abhishek D Garg (1) , Ann Smeets (29) , Diether Lambrechts (1) , Elia Biganzoli (30) , François Richard (1) , Christine Desmedt (1)

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

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.

Domaines: Cancer; Génétique humaine; Endocrinologie et métabolisme; Santé publique et épidémiologie

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⟩