Abstract
TP53 activation by genotoxic drugs can induce apoptosis or cell-cycle arrest. Thus, whether the gene is mutated or wild type could affect the response of a tumour to chemotherapy. Clinical data are unclear, possibly as a result of heterogeneity of tumours, drugs, methods of assessing response, or TP53 status. We studied 50 non-inflammatory, locally advanced breast cancers that had been treated with high doses of a combination of epirubicin and cyclophosphamide. We noted eight complete responses, which all occurred in the 14 patients with tumours containing mutated TP53 (p<0.0001). In high-grade, advanced breast cancers, inactivation of the TP53 pathway could greatly improve the response to this chemotherapy regimen.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Apoptosis / drug effects
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Apoptosis / genetics
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Breast Neoplasms / drug therapy
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Breast Neoplasms / genetics*
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Breast Neoplasms / pathology
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Cell Death / drug effects
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Cell Death / genetics
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Cyclophosphamide / administration & dosage
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Cyclophosphamide / adverse effects
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DNA Mutational Analysis
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Dose-Response Relationship, Drug
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Drug Administration Schedule
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Epirubicin / administration & dosage
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Epirubicin / adverse effects
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Female
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Humans
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Middle Aged
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Neoplasm Staging
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Prognosis
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Treatment Outcome
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Tumor Suppressor Protein p53 / genetics*
Substances
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Tumor Suppressor Protein p53
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Epirubicin
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Cyclophosphamide