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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{"title"=>"Predictive and prognostic impact of TP53 mutations and MDM2 promoter genotype in primary breast cancer patients treated with epirubicin or paclitaxel", "type"=>"journal", "authors"=>[{"first_name"=>"Ranjan", "last_name"=>"Chrisanthar", "scopus_author_id"=>"56618561600"}, {"first_name"=>"Stian", "last_name"=>"Knappskog", "scopus_author_id"=>"15055995400"}, {"first_name"=>"Erik", "last_name"=>"Løkkevik", "scopus_author_id"=>"15056383900"}, {"first_name"=>"Gun", "last_name"=>"Anker", "scopus_author_id"=>"6701677944"}, {"first_name"=>"Bjørn", "last_name"=>"Østenstad", "scopus_author_id"=>"6701625645"}, {"first_name"=>"Steinar", "last_name"=>"Lundgren", "scopus_author_id"=>"7006290789"}, {"first_name"=>"Terje", "last_name"=>"Risberg", "scopus_author_id"=>"7004186810"}, {"first_name"=>"Ingvil", "last_name"=>"Mjaaland", "scopus_author_id"=>"6603240393"}, {"first_name"=>"Gudbrand", "last_name"=>"Skjønsberg", "scopus_author_id"=>"6504182063"}, {"first_name"=>"Turid", "last_name"=>"Aas", "scopus_author_id"=>"6701844930"}, {"first_name"=>"Ellen", "last_name"=>"Schlichting", "scopus_author_id"=>"7004233636"}, {"first_name"=>"Hans E.", "last_name"=>"Fjösne", "scopus_author_id"=>"6603715992"}, {"first_name"=>"Arne", "last_name"=>"Nysted", "scopus_author_id"=>"6603170276"}, {"first_name"=>"Johan Richard", "last_name"=>"Lillehaug", "scopus_author_id"=>"35601260500"}, {"first_name"=>"Per Eystein", "last_name"=>"Lønning", "scopus_author_id"=>"7006037579"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"21556366", "scopus"=>"2-s2.0-79955701699", "sgr"=>"79955701699", "doi"=>"10.1371/journal.pone.0019249", "pui"=>"361717712", "issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)\\n1932-6203 (Linking)"}, "id"=>"a6539828-eda7-38bf-b20f-c28a0fdfc54a", "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 wild-type 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.\\n\\nEXPERIMENTAL DESIGN: Each patient was randomly assigned to treatment with epirubicin 90 mg/m(2) (n = 109) or paclitaxel 200 mg/m(2) (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.\\n\\nPRINCIPAL 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).\\n\\nCONCLUSION: 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.", "link"=>"http://www.mendeley.com/research/predictive-prognostic-impact-tp53-mutations-mdm2-promoter-genotype-primary-breast-cancer-patients-tr", "reader_count"=>33, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Librarian"=>1, "Researcher"=>4, "Student > Ph. D. Student"=>9, "Student > Postgraduate"=>2, "Student > Master"=>7, "Other"=>2, "Student > Bachelor"=>5, "Professor"=>1, "Unspecified"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Librarian"=>1, "Researcher"=>4, "Student > Ph. D. Student"=>9, "Student > Postgraduate"=>2, "Student > Master"=>7, "Other"=>2, "Student > Bachelor"=>5, "Professor"=>1, "Unspecified"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>2, "Mathematics"=>1, "Agricultural and Biological Sciences"=>12, "Medicine and Dentistry"=>13, "Chemistry"=>1, "Social Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>13}, "Chemistry"=>{"Chemistry"=>1}, "Social Sciences"=>{"Social Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>12}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>3}}, "reader_count_by_country"=>{"Canada"=>1, "Norway"=>2, "Uruguay"=>1, "Mexico"=>1, "Portugal"=>1, "Russia"=>1}, "group_count"=>3}

Scopus | Further Information

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  • {"files"=>["https://ndownloader.figshare.com/files/391025", "https://ndownloader.figshare.com/files/391074", "https://ndownloader.figshare.com/files/391123", "https://ndownloader.figshare.com/files/391140", "https://ndownloader.figshare.com/files/391161", "https://ndownloader.figshare.com/files/391178", "https://ndownloader.figshare.com/files/391329"], "description"=>"<div><h3>Background</h3><p><em>TP53</em> mutations have been associated with resistance to anthracyclines but not to taxanes in breast cancer patients. The <em>MDM2</em> promoter single nucleotide polymorphism (SNP) T309G increases <em>MDM2</em> activity and may reduce wild-type p53 protein activity. Here, we explored the predictive and prognostic value of <em>TP53</em> and <em>CHEK2</em> mutation status together with <em>MDM2</em> SNP309 genotype in stage III breast cancer patients receiving paclitaxel or epirubicin monotherapy.</p> <h3>Experimental Design</h3><p>Each patient was randomly assigned to treatment with epirubicin 90 mg/m<sup>2</sup> (n = 109) or paclitaxel 200 mg/m<sup>2</sup> (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.</p> <h3>Principal Findings</h3><p>While <em>TP53</em> and <em>CHEK2</em> mutations predicted resistance to epirubicin, <em>MDM2</em> status did not. Neither <em>TP53/CHEK2</em> mutations nor <em>MDM2</em> status was associated with paclitaxel response. Remarkably, <em>TP53</em> mutations (p = 0.007) but also <em>MDM2</em> 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 <em>MDM2</em> status was observed among individuals harbouring wild-type <em>TP53</em> (p = 0.039) but not among individuals with <em>TP53</em> mutated tumors (p>0.5).</p> <h3>Conclusion</h3><p><em>TP53</em> and <em>CHEK2</em> mutations were associated with lack of response to epirubicin monotherapy. In contrast, <em>TP53</em> mutations and <em>MDM2</em> 309G allele status conferred poor disease-specific survival among patients treated with primary paclitaxel but not epirubicin monotherapy.</p> </div>", "links"=>[], "tags"=>["predictive", "prognostic", "mutations", "promoter", "genotype", "cancer", "patients", "treated", "epirubicin", "paclitaxel"], "article_id"=>137233, "categories"=>["Cancer", "Genetics"], "users"=>["Ranjan Chrisanthar", "Stian Knappskog", "Erik Løkkevik", "Gun Anker", "Bjørn Østenstad", "Steinar Lundgren", "Terje Risberg", "Ingvil Mjaaland", "Gudbrand Skjønsberg", "Turid Aas", "Ellen Schlichting", "Hans E. Fjösne", "Arne Nysted", "Johan Richard Lillehaug", "Per Eystein Lønning"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0019249.s001", "https://dx.doi.org/10.1371/journal.pone.0019249.s002", "https://dx.doi.org/10.1371/journal.pone.0019249.s003", "https://dx.doi.org/10.1371/journal.pone.0019249.s004", "https://dx.doi.org/10.1371/journal.pone.0019249.s005", "https://dx.doi.org/10.1371/journal.pone.0019249.s006", "https://dx.doi.org/10.1371/journal.pone.0019249.s007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Predictive_and_Prognostic_Impact_of_TP53_Mutations_and_MDM2_Promoter_Genotype_in_Primary_Breast_Cancer_Patients_Treated_with_Epirubicin_or_Paclitaxel/137233", "title"=>"Predictive and Prognostic Impact of <em>TP53</em> Mutations and <em>MDM2</em> Promoter Genotype in Primary Breast Cancer Patients Treated with Epirubicin or Paclitaxel", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-04-27 02:00:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/780171"], "description"=>"<p>A, Difference between the treatment arms; B, Difference in respect to <i>TP53</i> mutation status; C, Difference in respect to <i>TP53</i> mutation status in paclitaxel arm; D, Difference in respect to <i>TP53</i> mutation status in epirubicin arm.</p>", "links"=>[], "tags"=>["curves", "relapse-free", "disease-specific"], "article_id"=>450522, "categories"=>["Cancer", "Genetics"], "users"=>["Ranjan Chrisanthar", "Stian Knappskog", "Erik Løkkevik", "Gun Anker", "Bjørn Østenstad", "Steinar Lundgren", "Terje Risberg", "Ingvil Mjaaland", "Gudbrand Skjønsberg", "Turid Aas", "Ellen Schlichting", "Hans E. Fjösne", "Arne Nysted", "Johan Richard Lillehaug", "Per Eystein Lønning"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0019249.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Kaplan_Meier_curves_of_relapse_free_left_row_and_disease_specific_survival_right_row_/450522", "title"=>"Kaplan-Meier curves of relapse-free (left row) and disease-specific survival (right row).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-04-27 00:08:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/780274"], "description"=>"<p>A, Difference in respect to <i>MDM2 SNP309</i> status in sub-cohort of the patients harbouring wild-type <i>TP53</i>; B, Difference in respect to <i>MDM2 SNP309</i> variants when TG and GG were pooled in sub-cohort of the patients harbouring wild-type <i>TP53</i>; C, Difference in respect to <i>MDM2 SNP309</i> variants when TG and GG were pooled in paclitaxel arm. D; Difference in respect to <i>MDM2 SNP309</i> variant when TG and GG were pooled in epirubicin arm.</p>", "links"=>[], "tags"=>["curves", "relapse-free", "disease-specific"], "article_id"=>450626, "categories"=>["Cancer", "Genetics"], "users"=>["Ranjan Chrisanthar", "Stian Knappskog", "Erik Løkkevik", "Gun Anker", "Bjørn Østenstad", "Steinar Lundgren", "Terje Risberg", "Ingvil Mjaaland", "Gudbrand Skjønsberg", "Turid Aas", "Ellen Schlichting", "Hans E. Fjösne", "Arne Nysted", "Johan Richard Lillehaug", "Per Eystein Lønning"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0019249.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Kaplan_Meier_curves_of_relapse_free_left_row_and_disease_specific_survival_right_row_/450626", "title"=>"Kaplan-Meier curves of relapse-free (left row) and disease-specific survival (right row).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-04-27 00:10:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/780394"], "description"=>"<p><i>P</i><sup>1</sup>, with regard to clinical response comparing CR/PR/SD versus PD; <i>P</i><sup>2</sup>, with regard to clinical response comparing.</p><p>CR/PR versus SD/PD.</p>", "links"=>[], "tags"=>["chemotherapy"], "article_id"=>450752, "categories"=>["Cancer", "Genetics"], "users"=>["Ranjan Chrisanthar", "Stian Knappskog", "Erik Løkkevik", "Gun Anker", "Bjørn Østenstad", "Steinar Lundgren", "Terje Risberg", "Ingvil Mjaaland", "Gudbrand Skjønsberg", "Turid Aas", "Ellen Schlichting", "Hans E. Fjösne", "Arne Nysted", "Johan Richard Lillehaug", "Per Eystein Lønning"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0019249.t003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Distribution_according_to_response_to_chemotherapy_as_initial_and_second_treatment_/450752", "title"=>"Distribution according to response to chemotherapy as initial and second treatment.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-04-27 00:12:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/780443"], "description"=>"<p>Clinical response in relation to different parameters. <i>P</i><sup>1</sup>, with regard to clinical response comparing CR/PR/SD versus PD; <i>P</i><sup>2</sup>, with regard to clinical response comparing CR/PR versus PD;</p><p>*, In the subgroup of the patients revealing wild-type <i>TP53</i>.</p>", "links"=>[], "tags"=>["paclitaxel"], "article_id"=>450802, "categories"=>["Cancer", "Genetics"], "users"=>["Ranjan Chrisanthar", "Stian Knappskog", "Erik Løkkevik", "Gun Anker", "Bjørn Østenstad", "Steinar Lundgren", "Terje Risberg", "Ingvil Mjaaland", "Gudbrand Skjønsberg", "Turid Aas", "Ellen Schlichting", "Hans E. Fjösne", "Arne Nysted", "Johan Richard Lillehaug", "Per Eystein Lønning"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0019249.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinical_response_to_paclitaxel_in_relation_to_different_parameters_/450802", "title"=>"Clinical response to paclitaxel in relation to different parameters.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-04-27 00:13:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/780495"], "description"=>"<p>*One patient was erroneously enrolled with stage II disease.</p>", "links"=>[], "tags"=>["characteristics", "genotypes"], "article_id"=>450851, "categories"=>["Cancer", "Genetics"], "users"=>["Ranjan Chrisanthar", "Stian Knappskog", "Erik Løkkevik", "Gun Anker", "Bjørn Østenstad", "Steinar Lundgren", "Terje Risberg", "Ingvil Mjaaland", "Gudbrand Skjønsberg", "Turid Aas", "Ellen Schlichting", "Hans E. Fjösne", "Arne Nysted", "Johan Richard Lillehaug", "Per Eystein Lønning"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0019249.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinicopathological_characteristics_and_distribution_of_genotypes_analysed_/450851", "title"=>"Clinicopathological characteristics and distribution of genotypes analysed.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-04-27 00:14:11"}

PMC Usage Stats | Further Information

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Relative Metric

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