Blueprints of disease: precision platforms for modelling breast cancer

Lutz, C. (2026)

Doctoral Thesis

Breast cancer (BC) is a clinically and biologically heterogeneous disease. Luminal BC, the most prevalent subtype, is characterised by its dependence on hormones and presents ongoing challenges for treatment stratification and mechanistic understanding, in large part due to the lack of clinically relevant models. The overarching aim of this thesis is to develop, refine, and apply diverse preclinical modelling platforms to interrogate the drivers of luminal BC progression, heterogeneity, and therapeutic response. By combining in vivo modelling, genomic engineering, and large-scale phenotypic profiling, this work provides novel tools and insights into the functional biology of luminal BC. The thesis is structured around multiple platform modelling strategies, each applying new and refined techniques to address complementary aspects of (luminal) BC modelling and tumour biology.

• Breast cancer
• Modelling
• In vivo models
• Somatic engineering
• Hormone receptor
• Oestrogen
• Treatment resistance
• Cancer progression
• Xenografts
• Base editing

• All authors: Lutz, C.
• Supervisor: Jonkers, J.M.M.
• Co-supervisor: Messal, H.A.
• Committee: Lange, E.C.M. de; Visser, K.E. de; Rheenen, J. van; Martens, J.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2026-03-10
• ISBN (print): 9789464965483
• DOI: doi:10.60602/1887-4296062
• Sponsorship: The research described in this thesis was performed at the division of Molecular Pathology at the Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital (NKI-AvL) (Amsterdam, The Netherlands). The research was financially supported by Cancer Research UK, KWF Kankerbestrijding, and Oncode Institute.