Annals of Oncology Advance Access originally published online on March 17, 2007
Annals of Oncology 2007 18(6):997-1003; doi:10.1093/annonc/mdm075
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2007 European Society for Medical Oncology
breast cancer |
p-53 gene mutations as a predictive marker in a population of advanced breast cancer patients randomly treated with doxorubicin or docetaxel in the context of a phase III clinical trial
1 Medical Oncology, Sandro Pitigliani Hospital of Prato, Prato, Italy
2 Medical Oncology, University Hospital of Tampere, Tampere, Finland
3 Translational Research Unit, Institute Jules Bordet, Bruxelles, Belgium
4 Clinical Oncology, City Hospital, Nottingham, United Kingdom
5 Medical Oncology, St. James University Hospital, Leeds, United Kingdom
6 Oncology, Clinique De Genolier, Genolier, Switzerland
7 Pathology, Institute Jules Bordet, Bruxelles, Belgium
8 Institute of Medical Technology, University of Tampere, Tampere, Finland
* Correspondence to: Dr A. Di Leo, Department of Oncology, "Sandro Pitigliani" Medical Oncology Unit, Hospital of Prato, Tuscany Cancer Institute, Piazza dell'Ospedale 2, 59100, Prato, Italy. Tel: +39-0574-434766; Fax: +39-0574-29798; E-mail: adileo{at}usl4.toscana.it
Background: Preclinical data indicate that p-53 gene mutations predict resistance to doxorubicin (A) but not to docetaxel (Taxotere) (T). In the TAX 303 trial, A and T have been compared with advanced breast cancer patients.
Patients and methods: Primary tumor samples from patients participating in the TAX 303 trial were collected. p-53 gene mutations were evaluated by denaturing high-performance liquid chromatography (DHPLC) and confirmed by sequencing. Topoisomerase II alpha (topo II 
) protein levels were evaluated by immunohistochemistry. Clinical and biological data were correlated.
Results: Tumor samples for DHPLC analysis were available for 108 of 326 patients from the clinical trial. p-53 gene mutations were observed in 20% of patients. In patients with a mutated p-53 gene, a trend for a lower percentage of responders was observed in the A arm (17%) compared with the T arm (50%). In the wild-type p-53 cohort, response rates to A and T were 27% and 36%, respectively.
Of the 16 patients carrying wild-type p-53- and topo II protein-positive tumors, seven (44%) responded to anthracyclines, while response rate to the same drug was 13% in the remaining cohorts [odds ratio 5.06 (95% confidence interval 1.19–21.41), P = 0.03]. The combination of the two markers had no predictive value in patients treated with docetaxel.
Conclusions: (i) p-53 gene analysis indicates that gene mutations may compromise the efficacy of A while they do not interfere with the antitumor activity of T; and (ii) the evaluation of multiple molecular markers including p-53 and proliferation markers as topo II protein levels looks more promising in predicting response to anthracyclines.
Key words: cytotoxics, molecular markers, topoisomerase II alpha
Received for publication October 5, 2006. Revision received February 1, 2007. Accepted for publication February 2, 2007.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Morabito, M. C. Piccirillo, K. Monaco, C. Pacilio, F. Nuzzo, P. Chiodini, C. Gallo, A. de Matteis, F. Perrone, and NCI Naples Breast Cancer Group First-Line Chemotherapy for HER-2 Negative Metastatic Breast Cancer Patients Who Received Anthracyclines as Adjuvant Treatment Oncologist, November 1, 2007; 12(11): 1288 - 1298. [Abstract] [Full Text] [PDF]
|
|