• 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 ...
    • Disseminated tumor cells as selection marker and monitoring tool for secondary adjuvant treatment in early breast cancer. Descriptive results from an intervention study 

      Synnestvedt, Marit; Borgen, Elin; Wist, Erik; Wiedswang, Gro; Weyde, Kjetil; Risberg, Terje; Kersten, Christian; Mjaaland, Ingvil; Vindi, Lise; Schirmer, Cecilie; Nesland, Jahn M; Naume, Bjørn (Journal article; Tidsskriftartikkel; Peer reviewed, 2012-12-22)
      Background: Presence of disseminated tumor cells (DTCs) in bone marrow (BM) after completion of systemic adjuvant treatment predicts reduced survival in breast cancer. The present study explores the use of DTCs to identify adjuvant insufficiently treated patients to be offered secondary adjuvant treatment intervention, and as a surrogate marker for therapy response.<p> <p>Methods: A total of ...
    • 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 ...
    • Low Z-4OHtam concentrations are associated with adverse clinical outcome among early stage premenopausal breast cancer patients treated with adjuvant tamoxifen 

      Helland, Thomas; Naume, Bjørn; Hustad, Steinar; Bifulco, Ersilia; Kvaløy, Jan Terje; Sætersdal, Anna Barbro; Synnestvedt, Marit; Lende, Tone Hoel; Gilje, Bjørnar; Mjaaland, Ingvil; Weyde, Kjetil; Blix, Egil Støre; Wiedswang, Gro; Borgen, Elin; Hertz, Daniel Louis; Janssen, Emiel; Mellgren, Gunnar; Søiland, Håvard (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-12-14)
      Abstract Low steady‐state levels of active tamoxifen metabolites have been associated with inferior treatment outcomes. In this retrospective analysis of 406 estrogen receptor‐positive breast cancer (BC) patients receiving adjuvant tamoxifen as initial treatment, we have associated our previously reported thresholds for the two active metabolites, Z‐endoxifen and Z‐4‐hydroxy‐tamoxifen (Z‐4OHtam), ...
    • 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 ...