• CHEK2 Mutations Affecting Kinase Activity Together With Mutations in TP53 Indicate a Functional Pathway Associated with Resistance to Epirubicin in Primary Breast Cancer 

      Chrisanthar, Ranjan; Knappskog, Stian; Løkkevik, Erik; Anker, Gun; Østenstad, Bjørn; Lundgren, Steinar; Berge, Elisabet O.; Risberg, Terje; Mjaaland, Ingvil; Mæhle, Lovise; Engebretsen, Lars Fredrik; Lillehaug, Johan Richard; Lønning, Per Eystein (Journal article; Tidsskriftartikkel; Peer reviewed, 2008-08-26)
      Background Chemoresistance is the main obstacle to cure in most malignant diseases. Anthracyclines are among the main drugs used for breast cancer therapy and in many other malignant conditions. Single parameter analysis or global gene expression profiles have failed to identify mechanisms causing in vivo resistance to anthracyclines. While we previously found TP53 mutations in the L2/L3 domains to ...
    • Concomitant inactivation of the p53- and pRB- functional pathways predicts resistance to DNA damaging drugs in breast cancer in vivo 

      Knappskog, Stian; Berge, Elisabet Ognedal; Chrisanthar, Ranjan; Geisler, Stephanie; Staalesen, Vidar; Leirvaag, Beryl; Yndestad, Synnøve; de Faveri, Elise Norheim; Karlsen, Bård Ove; Wedge, David C.; Akslen, Lars A.; Lilleng, Peer Kåre; Løkkevik, Erik; Lundgren, Steinar; Østenstad, Bjørn; Risberg, Terje; Mjaaland, Ingvil; Aas, Turid; Lønning, Per Eystein (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-05-08)
      Chemoresistance is the main obstacle to cancer cure. Contrasting studies focusing on single gene mutations, we hypothesize chemoresistance to be due to inactivation of key pathways affecting cellular mechanisms such as apoptosis, senescence, or DNA repair. In support of this hypothesis, we have previously shown inactivation of either TP53 or its key activators CHK2 and ATM to predict resistance ...
    • Homologous Recombination Deficiency Across Subtypes of Primary Breast Cancer 

      Yndestad, Synnøve; Engebrethsen, Christina; Herencia-Ropero, A.; Nikolaienko, Oleksii; Vintermyr, Olav Karsten; Lillestøl, Reidun Kristine; Minsaas, Laura; Leirvaag, Beryl; Iversen, Gjertrud Titlestad; Gilje, Bjørnar; Blix, Egil Støre; Espelid, Helge; Lundgren, Steinar; Geisler, Jürgen; Aase, Hildegunn Siv; Aas, Turid; Gudlaugsson, Einar; Llop-Guevara, Alba; Serra, Violeta; Janssen, Emiel; Lønning, Per Eystein; Knappskog, Stian; Eikesdal, Hans Petter (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-12-01)
      Purpose - Homologous recombination deficiency (HRD) is highly prevalent in triple-negative breast cancer (TNBC) and associated with response to PARP inhibition (PARPi). Here, we studied the prevalence of HRD in non-TNBC to assess the potential for PARPi in a wider group of patients with breast cancer.<p> <p>Methods - HRD status was established using targeted gene panel sequencing (360 genes) and ...
    • Low expression levels of ATM may substitute for CHEK2/TP53 mutations predicting resistance towards anthracycline and mitomycin chemotherapy in breast cancer 

      Knappskog, Stian; Chrisanthar, Ranjan; Løkkevik, Erik; Anker, Gun Birgitta; Østenstad, Bjørn; Lundgren, Steinar; Risberg, Terje; Mjaaland, Ingvil; Leirvaag, Beryl; Miletic, Hrvoje; Lønning, Per Eystein (Journal article; Tidsskriftartikkel; Peer reviewed, 2012-03-15)
      <i>Introduction</i>: Mutations affecting p53 or its upstream activator Chk2 are associated with resistance to DNA-damaging chemotherapy in breast cancer. ATM (Ataxia Telangiectasia Mutated protein) is the key activator of p53 and Chk2 in response to genotoxic stress. Here, we sought to evaluate ATM's potential role in resistance to chemotherapy.<p> <p><i>Methods</i>: We sequenced <i>ATM</i> and ...
    • Ny medikamentell behandling av brystkreft - Adjuvant behandling med trastuzumab ved tidlig stadium av brystkreft 

      Johansen, Karianne; Lønning, Per Eystein; Naume, Bjørn; Norderhaug, Inger Natvig; Norum, Jan; Olsen, Jan Abel; Wist, Erik (Research report; Forskningsrapport, 2006)
      Denne rapporten er første del av et oppdrag fra Sosial- og helsedirektoratet og RHF - fagdirektørene med fokus på effekt og bivirkninger av virkestoffet trastuzumab ved adjuvant behandling av brystkreft. Trastuzumab er ofte omtalt ved produktnavnet Herceptin.
    • Ny medikamentell behandling av brystkreft Adjuvant behandling med trastuzumab ved tidlig stadium av brystkreft - en helseøkonomisk analyse 

      Johansen, Karianne; Wisløff, Torbjørn; Kristiansen, Ivar Sønbø; Lønning, Per Eystein; Naume, Bjørn; Norum, Jan; Norderhaug, Inger Natvig; Olsen, Jan Abel; Wist, Erik (Research report; Forskningsrapport, 2006)
      Denne rapporten er andre del av et oppdrag fra Sosial- og helsedirektoratet og RHF - fagdirektørene med fokus på virkestoffet trastuzumab ved adjuvant behandling av brystkreft. Adjuvant behandling gis i tillegg til hovedbehandlingen (for eksempel kirurgi) for å påvirke eventuelt gjenværende kreftceller hos pasienten. Denne delen av oppdraget vurderer de helseøkonomiske konsekvensene av adjuvant ...
    • Olaparib monotherapy as primary treatment in unselected triple negative breast cancer 

      Eikesdal, Hans Petter; Yndestad, Synnøve; Elzawahry, Asmaa; Llop-Guevara, Alba; Gilje, Bjørnar; Blix, Egil Støre; Espelid, Helge; Lundgren, Steinar; Geisler, Jürgen; Vagstad, Geirfinn; Venizelos, Andreas; Minsaas, Laura; Leirvaag, Beryl; Gudlaugsson, Einar; Vintermyr, Olav Karsten; Aase, Hildegunn Siv; Aas, Turid; Balmaña, Judith; Serra, Violeta; Janssen, Emiel; Knappskog, Stian; Lønning, Per Eystein (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-11-23)
      <p><i>Background - </i>The antitumor efficacy of PARP inhibitors (PARPi) for breast cancer patients harboring germline BRCA1/2 (gBRCA1/2) mutations is well established. While PARPi monotherapy was ineffective in patients with metastatic triple negative breast cancer (TNBC) wild type for BRCA1/2, we hypothesized that PARPi may be effective in primary TNBCs without previous chemotherapy exposure. < ...
    • Persistence of disseminated tumor cells after neoadjuvant treatment for locally advanced breast cancer predicts poor survival 

      Mathiesen, Randi Margit Ruud; Borgen, Elin; Renolen, Anne; Løkkevik, Erik; Nesland, Jahn M; Anker, Gun Birgitta; Østenstad, Bjørn; Lundgren, Steinar; Risberg, Terje; Mjaaland, Ingvil; Kvalheim, Gunnar; Lønning, Per Eystein; Naume, Bjørn (Journal article; Tidsskriftartikkel; Peer reviewed, 2012-08-14)
      <i>Introduction</i> - Presence of disseminated tumor cells (DTCs) in bone marrow (BM) and circulating tumor cells (CTC) in peripheral blood (PB) predicts reduced survival in early breast cancer. The aim of this study was to determine the presence of and alterations in DTC- and CTC-status in locally advanced breast cancer patients undergoing neoadjuvant chemotherapy (NACT) and to evaluate their ...
    • Predictive and Prognostic Impact of TP53 Mutations and MDM2 Promoter Genotype in Primary Breast Cancer Patients Treated with Epirubicin or Paclitaxel 

      Chrisanthar, Ranjan; Knappskog, Stian; Løkkevik, Erik; Anker, Gun Birgitta; Østenstad, Bjørn; Lundgren, Steinar; Risberg, Terje; Mjaaland, Ingvil; Skjønsberg, Gudbrand; Aas, Turid; Schlichting, Ellen; Fjøsne, Hans Erikssønn; Nysted, Arne; Lillehaug, Johan R.; Lønning, Per Eystein (Journal article; Tidsskriftartikkel; Peer reviewed, 2011)
      TP53 mutations have been associated with resistance to anthracyclines but not to taxanes in breast cancer patients. The MDM2 promoter single nucleotide polymorphism (SNP) T309G increases MDM2 activity and may reduce wildtype p53 protein activity. Here, we explored the predictive and prognostic value of TP53 and CHEK2 mutation status together with MDM2 SNP309 genotype in stage III breast cancer ...