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 KrishnamurthySunil 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 (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    9 Citations (Scopus)
    56 Downloads (Pure)

    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.

    Original languageEnglish
    Article number4418
    Number of pages17
    JournalNature Communications
    Volume14
    Early online date21 Jul 2023
    DOIs
    Publication statusPublished - 2023

    Keywords

    • Breast cancer
    • Cancer genomics
    • Tumour heterogeneity

    ASJC Scopus subject areas

    • General Chemistry
    • General Biochemistry,Genetics and Molecular Biology
    • General Physics and Astronomy

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