Obesity-associated changes in molecular biology of primary breast cancer

Nguyen, Ha-Linh; Geukens, Tatjana; Maetens, Marion; Aparicio, Samuel; Bassez, Ayse; Borg, Ake; Brock, Jane; Broeks, Annegien; Caldas, Carlos; Cardoso, Fatima; De Schepper, Maxim; Delorenzi, Mauro; Drukker, Caroline A.; Glas, Annuska M.; Green, Andrew R.; Isnaldi, Edoardo; Eyfjörð, Jórunn; Khout, Hazem; Knappskog, Stian; Krishnamurthy, Savitri; Lakhani, Sunil R.; Langerod, Anita; Martens, John W. M.; McCart Reed, Amy E.; Murphy, Leigh; Naulaerts, Stefan; Nik-Zainal, Serena; Nevelsteen, Ines; Neven, Patrick; Piccart, Martine; Poncet, Coralie; Punie, Kevin; Purdie, Colin; Rakha, Emad A.; Richardson, Andrea; Rutgers, Emiel; Vincent-Salomon, Anne; Simpson, Peter T.; Schmidt, Marjanka K.; Sotiriou, Christos; Span, Paul N.; Tan, Kiat Tee Benita; Thompson, Alastair; Tommasi, Stefania; Van Baelen, Karen; Van de Vijver, Marc; Van Laere, Steven; van’t Veer, Laura; Viale, Giuseppe; Viari, Alain; Vos, Hanne; Witteveen, Anke T.; Wildiers, Hans; Floris, Giuseppe; Garg, Abhishek D.; Smeets, Ann; Lambr...

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.

Citation

Nguyen, H.-L., Geukens, T., Maetens, M., Aparicio, S., Bassez, A., Borg, A., Brock, J., Broeks, A., Caldas, C., Cardoso, F., De Schepper, M., Delorenzi, M., Drukker, C. A., Glas, A. M., Green, A. R., Isnaldi, E., Eyfjörð, J., Khout, H., Knappskog, S., Krishnamurthy, S., …Desmedt, C. (2023). Obesity-associated changes in molecular biology of primary breast cancer. Nature Communications, 14, Article 4418. https://doi.org/10.1038/s41467-023-39996-z

• Journal Article Type: Article
• Acceptance Date: Jul 6, 2023
• Online Publication Date: Jul 21, 2023
• Publication Date: Jul 21, 2023
• Deposit Date: Jul 24, 2023
• Publicly Available Date: Jul 24, 2023
• Journal: Nature Communications
• Electronic ISSN: 2041-1723
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 14
• Article Number: 4418
• DOI: https://doi.org/10.1038/s41467-023-39996-z
• Keywords: General Physics and Astronomy; General Biochemistry, Genetics and Molecular Biology; General Chemistry; Multidisciplinary
• Public URL: https://nottingham-repository.worktribe.com/output/23439873
• Publisher URL: https://www.nature.com/articles/s41467-023-39996-z
• Additional Information: Received: 24 January 2023; Accepted: 6 July 2023; First Online: 21 July 2023; : Ethical approval was granted for each of the source studies. Data were acquired for the purpose of this study through publications and open-access data portals for the ICGC, METABRIC, and ELBC cohorts. Ethical compliance for the use of data from the MINDACTand BioKey cohorts was ensured through a Data Transfer Agreement approved by the EORTCand UZ Leuven-VIB, respectively.; : The authors declare no competing interests.