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Predictive and Prognostic Impact of TP53 Mutations and MDM2 Promoter Genotype in Primary Breast Cancer Patients Treated with Epirubicin or Paclitaxel

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dc.contributor.author Chrisanthar, Ranjan eng
dc.contributor.author Knappskog, Stian eng
dc.contributor.author Løkkevik, Erik eng
dc.contributor.author Anker, Gun Birgitta eng
dc.contributor.author Østenstad, Bjørn eng
dc.contributor.author Lundgren, Steinar eng
dc.contributor.author Risberg, Terje eng
dc.contributor.author Mjaaland, Ingvil eng
dc.contributor.author Skjønsberg, Gudbrand eng
dc.contributor.author Aas, Turid eng
dc.contributor.author Schlichting, Ellen eng
dc.contributor.author Fjösne, Hans E. eng
dc.contributor.author Nysted, Arne eng
dc.contributor.author Lillehaug, Johan eng
dc.contributor.author Lønning, Per Eystein eng
dc.date.accessioned 2012-02-27T13:43:28Z
dc.date.available 2012-02-27T13:43:28Z
dc.date.issued 2011-04-27 eng
dc.identifier.citation PLoS ONE 6(4): e19249 en
dc.identifier.issn 1932-6203 eng
dc.identifier.uri http://hdl.handle.net/1956/5648
dc.description.abstract Background: 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 patients receiving paclitaxel or epirubicin monotherapy. Experimental Design: Each patient was randomly assigned to treatment with epirubicin 90 mg/m2 (n= 109) or paclitaxel 200 mg/m2 (n = 114) every 3rd week as monotherapy for 4–6 cycles. Patients obtaining a suboptimal response on first-line treatment requiring further chemotherapy received the opposite regimen. Time from last patient inclusion to follow-up censoring was 69 months. Each patient had snap-frozen tumor tissue specimens collected prior to commencing chemotherapy. Principal Findings: While TP53 and CHEK2 mutations predicted resistance to epirubicin, MDM2 status did not. Neither TP53/ CHEK2 mutations nor MDM2 status was associated with paclitaxel response. Remarkably, TP53 mutations (p = 0.007) but also MDM2 309TG/GG genotype status (p = 0.012) were associated with a poor disease-specific survival among patients having paclitaxel but not patients having epirubicin first-line. The effect of MDM2 status was observed among individuals harbouring wild-type TP53 (p = 0.039) but not among individuals with TP53 mutated tumors (p.0.5). Conclusion: TP53 and CHEK2 mutations were associated with lack of response to epirubicin monotherapy. In contrast, TP53 mutations and MDM2 309G allele status conferred poor disease-specific survival among patients treated with primary paclitaxel but not epirubicin monotherapy. en
dc.language.iso eng eng
dc.publisher Public Library of Science eng
dc.rights Attribution CC BY eng
dc.rights.uri http://creativecommons.org/licenses/by/2.5/ eng
dc.title Predictive and Prognostic Impact of TP53 Mutations and MDM2 Promoter Genotype in Primary Breast Cancer Patients Treated with Epirubicin or Paclitaxel eng
dc.type Peer reviewed eng
dc.type Journal article eng
dc.subject.nsi VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762 eng
dc.rights.holder Copyright 2011 Chrisanthar et al.
dc.type.version publishedVersion eng
bora.peerreviewed Peer reviewed eng
bora.cristinID 839750 eng
bibo.doi http://dx.doi.org/10.1371/journal.pone.0019249 eng
dc.identifier.cristinID 839750 eng
dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0019249


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