The public defence will be held as a video conference over Zoom.
The defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.
Click here to participate in the public defence
Due to copyright reasons, an electronic copy of the thesis must be ordered from the faculty. In order for the faculty to have time to process the order, it must be received by the faculty no later than 2 days prior to the public defence. Orders received later than 2 days before the defence will not be processed. Inquiries regarding the thesis after the public defence must be addressed to the candidate.
Digital Trial Lecture - time and place
Adjudication committee
- First opponent: Professor Lisa Rydén, Lund University, Sweden
- Second opponent: Professor Elin Mortensen, UiT - The Arctic University of Norway, Tromsø
- Third member and chair of the evaluation committee: Professor Frode Lars Jahnsen, Institute of Clinical Medicine, University of Oslo
Chair of defence
Professor II Pål Dag Line, Institute of Clinical Medicine, University of Oslo
Principal supervisor
Associate Professor Olav Engebråten, Institute of Clinical Medicine, University of Oslo
Summary
More than 3400 women were diagnosed with breast cancer in Norway in 2020. About 12 % were diagnosed with primary inoperable breast cancer and are candidates for neoadjuvant treatment (i.e. treatment before surgery). For patients treated in clinical trials, the antiangiogenic agent bevacizumab combined with neoadjuvant chemotherapy significantly reduces the tumor size. Currently there are no available biomarkers for the prediction of long-term benefit to such therapy.
In this thesis, Hedda von der Lippe Gythfeldt and colleagues have performed analysis of clinical data and molecular data obtained from sequentially collected tumor biopsies in a neoadjuvant clinical trial of HER2-negative breast cancers.
Results from gene expression analysis of the tumor biopsies revealed an increased expression of immune genes in ER-positive tumors responding to the addition of bevacizumab. Furthermore, antiangiogenic combination treatment significantly increased the response rate in the ER-positive patient subset, and improved disease free survival in the patients with a complete or near-complete response to therapy, independent of ER-status.
Patients with triple-negative breast cancers did not demonstrate a benefit from antiangiogenic therapy and other therapeutic strategies are needed to improve the outcome of this patient group. Preclinical models may extend the molecular knowledge of the mechanisms behind response and resistance to therapy, and were therefore used to investigate the effect of a nuclear (liver-x-) receptor agonist in combination with chemotherapy. Treatment-induced changes in protein expression were analyzed in human breast tumors in vivo with a differential response to therapy.
Combination therapy with the nuclear receptor agonist resulted in reduced tumor proliferation in the preclinical experiments, and proteomic analysis revealed new insights into the mechanism behind the effect of nuclear receptors in triple-negative breast cancers.
The novel results presented in this thesis may impact the selection of patients most likely to benefit from antiangiogenic therapy, and adds to the knowledge about markers of response and resistance to treatment.
Additional information
contact the research support staff