Abstract
Functional p53 protein is essential for the cellular response to drug-induced DNA damage. We investigated p53 accumulation in tumour specimens from premenopausal breast cancer patients who were randomised to adjuvant chemotherapy (CMF) or postoperative radiotherapy. Of the tumours from 139 patients, 20 showed abnormal accumulation as judged with immunohistochemistry (> 10% positive tumour cells). The risk of distant recurrence was similar in the two treatment groups for patients whose primary tumours lacked p53 accumulation, whereas there was a significant benefit from CMF for patients showing abnormal accumulation (relative risk 0.18, 95% CI, 0.04-0.93). This result suggests that p53-dependent apoptosis is not a general mechanism by which breast cancer cells respond during CMF chemotherapy.
Publication types
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Clinical Trial
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Randomized Controlled Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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Aneuploidy
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Antimetabolites, Antineoplastic / administration & dosage
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Antineoplastic Agents, Alkylating / administration & dosage
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Antineoplastic Combined Chemotherapy Protocols / administration & dosage
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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 / radiotherapy
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Chemotherapy, Adjuvant
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Combined Modality Therapy
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Cyclophosphamide / administration & dosage
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DNA Damage
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DNA, Neoplasm / drug effects
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Female
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Fluorouracil / administration & dosage
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Gene Expression Regulation, Neoplastic*
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Humans
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Immunohistochemistry
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Mastectomy, Modified Radical
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Methotrexate / administration & dosage
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Neoplasm Recurrence, Local
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Postoperative Care
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Premenopause
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Risk Factors
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Tumor Suppressor Protein p53 / genetics*
Substances
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Antimetabolites, Antineoplastic
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Antineoplastic Agents, Alkylating
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DNA, Neoplasm
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Tumor Suppressor Protein p53
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Cyclophosphamide
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Fluorouracil
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Methotrexate