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Prognostic interaction between expression of p53 and estrogen receptor in patients with node-negative breast cancer : results from IBCSG Trials VIII and IX . INTRODUCTION The prognostic significance of p53 protein expression in early breast cancer remains uncertain , with some but not all studies finding an association with poorer outcomes . Estrogen receptor ( ER ) expression is both a positive prognostic marker and predictive of response to endocrine therapies . The relationship between these biomarkers is unknown . METHODS We constructed tissue microarrays ( TMAs ) from available pathological material from 1113 patients participating in two randomized clinical trials comparing endocrine therapy alone versus chemo-endocrine therapy in node-negative breast cancer . Expression of p53 defined as > 10 % positive nuclei was analyzed together with prior immunohistochemical assays of ER performed at central pathological review of whole tumor sections . RESULTS ER was present ( i.e . > 1 % positive tumor cell nuclei ) in 80.1 % ( 880/1092 ) . p53 expression was significantly more frequent when ER was absent , 125/212 ( 59 % ) than when ER was present , 171/880 ( 19 % ) , p < 0.0001 . A significant qualitative interaction was observed such that p53 expression was associated with better disease-free survival ( DFS ) and overall survival ( OS ) among patients whose tumors did not express ER , but worse DFS and OS among patients whose tumors expressed ER . The interaction remained significant after allowance for pathologic variables , and treatment . Similar effects were seen when luminal and non-luminal intrinsic subtypes were compared . CONCLUSIONS Interpretation of the prognostic significance of p53 expression requires knowledge of concurrent expression of ER . The reason for the interaction between p53 and ER is unknown but may reflect qualitatively different p53 mutations underlying the p53 expression in tumors with or without ER expression . TRIAL REGISTRATION Current Controlled Trials ACTRN12607000037404 ( Trial VIII ) and ACTRN12607000029493 ( Trial IX ) .
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Intervention_Pharmacological
endocrine therapy alone
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Intervention_Pharmacological
chemo-endocrine therapy
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Outcome_Physical
expression of p53
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Outcome_Other
poorer outcomes .
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Outcome_Physical
Estrogen receptor ( ER ) expression
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Outcome_Physical
Expression of p53
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Outcome_Physical
ER
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Outcome_Physical
p53 expression
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Outcome_Mortality
disease-free survival ( DFS )
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Outcome_Mortality
overall survival ( OS )
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Outcome_Mortality
DFS
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Outcome_Mortality
OS
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Outcome_Physical
p53 expression
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Outcome_Physical
expression of ER .
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Outcome_Physical
p53 mutations
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Outcome_Physical
p53 expression
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Participant_Condition
node-negative breast cancer
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Participant_Sample-size
1113
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Participant_Condition
node-negative breast cancer