Nature Communications (Jul 2023)
Obesity-associated changes in molecular biology of primary breast cancer
- Ha-Linh Nguyen,
- Tatjana Geukens,
- Marion Maetens,
- Samuel Aparicio,
- Ayse Bassez,
- Ake Borg,
- Jane Brock,
- Annegien Broeks,
- Carlos Caldas,
- Fatima Cardoso,
- Maxim De Schepper,
- Mauro Delorenzi,
- Caroline A. Drukker,
- Annuska M. Glas,
- Andrew R. Green,
- Edoardo Isnaldi,
- Jórunn Eyfjörð,
- Hazem Khout,
- Stian Knappskog,
- Savitri Krishnamurthy,
- Sunil R. Lakhani,
- Anita Langerod,
- John W. M. Martens,
- Amy E. McCart Reed,
- Leigh Murphy,
- Stefan Naulaerts,
- Serena Nik-Zainal,
- Ines Nevelsteen,
- Patrick Neven,
- Martine Piccart,
- Coralie Poncet,
- Kevin Punie,
- Colin Purdie,
- Emad A. Rakha,
- Andrea Richardson,
- Emiel Rutgers,
- Anne Vincent-Salomon,
- Peter T. Simpson,
- Marjanka K. Schmidt,
- Christos Sotiriou,
- Paul N. Span,
- Kiat Tee Benita Tan,
- Alastair Thompson,
- Stefania Tommasi,
- Karen Van Baelen,
- Marc Van de Vijver,
- Steven Van Laere,
- Laura van’t Veer,
- Giuseppe Viale,
- Alain Viari,
- Hanne Vos,
- Anke T. Witteveen,
- Hans Wildiers,
- Giuseppe Floris,
- Abhishek D. Garg,
- Ann Smeets,
- Diether Lambrechts,
- Elia Biganzoli,
- François Richard,
- Christine Desmedt
Affiliations
- Ha-Linh Nguyen
- Laboratory for Translational Breast Cancer Research, Department of Oncology
- Tatjana Geukens
- Laboratory for Translational Breast Cancer Research, Department of Oncology
- Marion Maetens
- Laboratory for Translational Breast Cancer Research, Department of Oncology
- Samuel Aparicio
- Department of Molecular Oncology, BC Cancer Research Centre
- Ayse Bassez
- Laboratory for Translational Genetics, Department of Human Genetics
- Ake Borg
- Department of Clinical Sciences, Division of Oncology and Pathology, Lund University
- Jane Brock
- Department of Pathology, Brigham and Women’s Hospital
- Annegien Broeks
- Departments of Core Facility, Molecular Pathology and Biobanking, Antoni van Leeuwenhoek, the Netherlands Cancer Institute
- Carlos Caldas
- Cancer Research UK Cambridge Institute and Department of Oncology, Li Ka Shing Centre, University of Cambridge
- Fatima Cardoso
- Breast Unit, Champalimaud Clinical Center/Champalimaud Foundation
- Maxim De Schepper
- Laboratory for Translational Breast Cancer Research, Department of Oncology
- Mauro Delorenzi
- Department of Oncology, University of Lausanne
- Caroline A. Drukker
- Department of Surgical Oncology, Antoni van Leeuwenhoek Hospital
- Annuska M. Glas
- Agendia
- Andrew R. Green
- Nottingham Breast Cancer Research Centre, School of Medicine, University of Nottingham
- Edoardo Isnaldi
- Laboratory for Translational Breast Cancer Research, Department of Oncology
- Jórunn Eyfjörð
- BioMedical Center, School of Health Sciences, Faculty of Medicine, University of Iceland
- Hazem Khout
- Department of Breast Surgery, Glenfield Hospital, University Hospitals of Leicester NHS Trust
- Stian Knappskog
- Department of Clinical Science, Faculty of Medicine, University of Bergen
- Savitri Krishnamurthy
- Department of Pathology, The University of Texas MD Anderson Cancer Center
- Sunil R. Lakhani
- UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland
- Anita Langerod
- Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital
- John W. M. Martens
- Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Erasmus University Medical Center
- Amy E. McCart Reed
- UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland
- Leigh Murphy
- University of Manitoba and Cancer Care Manitoba Research Institute
- Stefan Naulaerts
- Laboratory of Cell Stress & Immunity, Department of Cellular & Molecular Medicine
- Serena Nik-Zainal
- Department of Medical Genetics, School of Clinical Medicine, University of Cambridge
- Ines Nevelsteen
- Department of Surgical Oncology, University Hospitals Leuven
- Patrick Neven
- Department of Gynecological Oncology, University Hospitals Leuven
- Martine Piccart
- Institut Jules Bordet and Université Libre de Bruxelles
- Coralie Poncet
- European Organisation for Research and Treatment of Cancer (EORTC) Headquarters
- Kevin Punie
- Department of General Medical Oncology and Multidisciplinary Breast Unit, Leuven Cancer Institute and University Hospitals Leuven
- Colin Purdie
- Department of Pathology, University of Dundee, NHS Tayside
- Emad A. Rakha
- Division of Cancer and Stem Cells, School of Medicine, University of Nottingham
- Andrea Richardson
- Johns Hopkins University School of Medicine
- Emiel Rutgers
- Department of Surgical Oncology, Netherlands Cancer Institute
- Anne Vincent-Salomon
- Diagnostic and Theranostic Medicine Division, Institut Curie, PSL Research University
- Peter T. Simpson
- UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland
- Marjanka K. Schmidt
- Division of Molecular Pathology, Netherlands Cancer Institute—Antoni van Leeuwenhoek Hospital
- Christos Sotiriou
- Institut Jules Bordet, Universite Libre de Bruxelles
- Paul N. Span
- Department of Radiation Oncology, Radboud University Medical Center
- Kiat Tee Benita Tan
- Department of General Surgery, Sengkang General Hospital
- Alastair Thompson
- Department of Surgery, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine
- Stefania Tommasi
- Molecular Diagnostics and Pharmacogenetics Unit, IRCCS Istituto Tumouri “Giovanni Paolo II”
- Karen Van Baelen
- Laboratory for Translational Breast Cancer Research, Department of Oncology
- Marc Van de Vijver
- Department of Pathology, Amsterdam University Medical Centers, Cancer Center Amsterdam, University of Amsterdam
- Steven Van Laere
- Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp
- Laura van’t Veer
- Department of Laboratory Medicine, UCSF Helen Diller Family Comprehensive Cancer Center
- Giuseppe Viale
- Division of Pathology, IEO, European Institute of Oncology IRCCS
- Alain Viari
- Synergie Lyon Cancer, Plateforme de Bio-informatique ‘Gilles Thomas’
- Hanne Vos
- Department of Surgical Oncology, University Hospitals Leuven
- Anke T. Witteveen
- Agendia
- Hans Wildiers
- Department of General Medical Oncology and Multidisciplinary Breast Unit, Leuven Cancer Institute and University Hospitals Leuven
- Giuseppe Floris
- Department of Pathology, University Hospitals Leuven
- Abhishek D. Garg
- Laboratory of Cell Stress & Immunity, Department of Cellular & Molecular Medicine
- Ann Smeets
- Department of Surgical Oncology, University Hospitals Leuven
- Diether Lambrechts
- Laboratory for Translational Genetics, Department of Human Genetics
- Elia Biganzoli
- Unit of Medical Statistics, Biometry and Epidemiology, Department of Biomedical and Clinical Sciences (DIBIC) “L. Sacco” & DSRC, LITA Vialba campus, Università degli Studi di Milano
- François Richard
- Laboratory for Translational Breast Cancer Research, Department of Oncology
- Christine Desmedt
- Laboratory for Translational Breast Cancer Research, Department of Oncology
- DOI
- https://doi.org/10.1038/s41467-023-39996-z
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 17
Abstract
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.
