Effect of mutated TP53 on response of advanced breast cancers to high-dose chemotherapy

Lancet. 2002 Sep 14;360(9336):852-4. doi: 10.1016/S0140-6736(02)09969-5.


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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Death / drug effects
  • Cell Death / genetics
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • DNA Mutational Analysis
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Epirubicin / administration & dosage
  • Epirubicin / adverse effects
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / genetics*


  • Tumor Suppressor Protein p53
  • Epirubicin
  • Cyclophosphamide