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Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Fernando Schmitt, University of Porto, Portugal
- Second opponent: Associate professor Marit Valla, Norwegian University of Science and Technology,
- Third member and chair of the evaluation committee: Professor Odd Terje Brustugun, University of Oslo
Chair of the Defence
Professor Jonn Terje Geitung, University of Oslo
Principal Supervisor
Professor Jürgen Geisler, University of Oslo
Summary
This thesis sheds light on the complex biology and potential impact on modern treatment of ductal carcinoma in-situ (DCIS), a precursor to invasive breast cancer, emphasizing the urgent need for personalized care.
Breast cancer remains the most common cancer among women worldwide and absorbs more healthcare resources than any other malignancy in wealthy countries. Thanks to screening programs, high-income nations have witnessed increasing breast cancer incidence but declining death rates, while the opposite trend persists in many low-income settings.
DCIS now makes up a substantial proportion of early breast cancer diagnoses, largely due to increased screening. This thesis adds new information to DCIS-biology indicating that one-size-fits-all treatments, as currently widely established, may not be optimal and could lead to unnecessary as well as insufficient interventions for selected patients.
We analyzed tissue samples from nearly 500 Norwegian women diagnosed with DCIS between 1996 and 2018, including 357 cases of high-grade DCIS. We performed immunohistochemistry to profile estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 proliferation index across various molecular subtypes. Our findings reveal that DCIS reflects the full spectrum of molecular subtypes as seen in invasive breast cancer, but their distribution can vary depending on the classification system used.
Notably, HER2-enriched cases were flagged as a potential high-risk subtype due to frequent associations with tumor invasion. The study results also showed that low PR levels combined with high Ki67 proliferation rates were significantly linked to HER2 overexpression.
A separate arm of the study measured pathologists’ agreement in scoring the Ki67 biomarker—key for risk assessment and clinical decisions. These results underscore how carefully tailored subtype-specific management holds promise for improving outcomes and reducing overtreatment for DCIS.
Despite huge leaps in immunotherapy for many advanced cancers, DCIS treatment has remained unchanged. This thesis sets the stage for future clinical protocols integrating advanced molecular profiling and precision medicine in early breast cancer care.
Additional information
Contact the research support staff.