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Lancet. 2002 Sep 14;360(9336):852-4.

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

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Service de Pathologie and INSERM ERM 0220, Hôpital Saint-Louis, 1 Ave C, Vellefaux, 75475 Paris, Cedex 10, France.


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.

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