The Department of Biomedicine

BBB webinar: Therese Sørlie

Breast cancer molecular subtypes and phenotypes in ductal carcinoma in situ (DCIS)

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Therese Sørlie
Institute for Cancer Research, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo

Since the discovery of the five intrinsic molecular breast tumor subtypes in early 2000, their clinical impact and usefulness has been proven in numerous studies, and they are today the foundations of the major classification scheme of breast cancer. Despite this delineation, breast tumors are intratumor heterogeneous, potentially adding complexity to a classification system. The difference between a bona fide subtype and a tumor phenotype might not be easily discerned. For example, we show that ‘claudin-low’ tumors express features reflective of their underlying intrinsic tumor subtype, and propose that claudin-low is a phenotype, which tumors may display in addition to their intrinsic breast cancer subtype. Similar heterogeneity exists in DCIS, hence these types of lesions can be subtyped using the same method. However, it is unclear whether the interpretation of the subtypes should be equal in DCIS and invasive breast cancer (IBC). Through our genomic analyses, we have found considerable differences in particular for the basal-like subtype that may indicate that basal-like DCIS may be a different tumor entity than basal-like IBC, or that the basal-like subtype may have a different meaning at the pre-invasive stage. Together, our studies emphasize the importance of taking a subtype specific approach when studying breast tumor progression and highlight important differences in tumor progression between molecular subtypes. Finally, a framework for precision modeling of the relation between DNA methylation, DNA copy number and gene expression will be presented, which is made available through a versatile online tool at https://shinyibv02.uio.no/panorama/

Chairperson: Gro Vatne Røsland, Department of Biomedicine