Effect of mutated TP53 on response of advanced breast cancers to high-dose chemotherapy.
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.
Bertheau
P
P
Service de Pathologie and INSERM ERM 0220, Hôpital Saint-Louis, 1 Ave C, Vellefaux, 75475 Paris, Cedex 10, France.
Plassa
F
F
Espié
M
M
Turpin
E
E
de Roquancourt
A
A
Marty
M
M
Lerebours
F
F
Beuzard
Y
Y
Janin
A
A
de Thé
H
H
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004252:DNA Mutational Analysis; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D016159:Tumor Suppressor Protein p53; D015251:Epirubicin; D003520:Cyclophosphamide