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Annals of Oncology Advance Access published online on March 31, 2005
Annals of Oncology, doi:10.1093/annonc/mdi150
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© 2005 European Society for Medical Oncology
Received September 3, 2004
Revised December 20, 2004
Accepted December 22, 2004

Original article

Worse survival for TP53 (p53)-mutated breast cancer patients receiving adjuvant CMF

J. Andersson 1*, L. Larsson 2, S. Klaar 1, L. Holmberg 3, J. Nilsson 3, M. Inganäs 4, G. Carlsson 2, J. Öhd 1, C.-M. Rudenstam 2, B. Gustavsson 2, and J. Bergh 1

1 Department of Oncology, Cancer Center Karolinska, Radiumhemmet, Karolinska Institute and University Hospital, Stockholm, Sweden
2 Department of Surgery, Östra Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden
3 Regional Oncological Center, University Hospital, Uppsala, Sweden
4 Gyros AB, Uppsala Science Park, Uppsala, Sweden

* To whom correspondence should be addressed.
J. Andersson, E-mail: jenny.andersson{at}cck.ki.se


  Abstract

Background: TP53 has been described as a prognostic factor in many malignancies, including breast cancer. Whether it also might be a predictive factor with reference to chemo- and endocrine therapy is more controversial.

Patients and methods: We investigated relapse-free (RFS), breast cancer-corrected (BCCS) and overall survival (OS) related to TP53 status in node-positive breast cancer patients that had received polychemotherapy [cyclophosphamide, methotrexate, 5-fluorouracil (CMF)] and/or endocrine therapy (tamoxifen). Sequence analyses of the whole TP53 coding region was performed in 376 patients operated on for primary breast cancer with axillary lymph node metastases between 1984 and 1989 (median follow-up time 84 months).

Results: TP53 mutations were found in 105 patients (28%). We found 90 (82%) of the 110 mutations in the more frequently analysed exons 5-8, while the other 20 (18%) were located in exons 3-4 and 9-10, respectively. Univariate analyses showed TP53 to be a significant prognostic factor with regard to RFS, BCCS and OS in patients who received adjuvant CMF.

Conclusions: TP53 mutations might induce resistance to certain modalities of breast cancer therapy. Sequence-determined TP53 mutation was of negative prognostic value in the total patient population and in the CMF treated patients.

Keywords: adjuvant therapy; CMF; p53; sequence-based analysis; tamoxifen; TP53.
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A Di Leo, M Tanner, C Desmedt, M Paesmans, F Cardoso, V Durbecq, S Chan, T Perren, M Aapro, C Sotiriou, et al.
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
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