Annals of Oncology 14:428-432, 2003
© 2003 European Society for Medical Oncology
Original Paper |
Correlation of p53 status with outcome of neoadjuvant chemotherapy using paclitaxel and doxorubicin in stage IIIB breast cancer
1 Department of Medical Oncology, Hospital do Câncer de São Paulo, São Paulo; 2 Ludwig Institute for Cancer Research, São Paulo, Brazil
Received 21 May 2002; revised 24 September; accepted 22 October 2002
Background:
The role of p53 in modulating apoptosis has suggested that it may affect efficacy of anticancer agents. We prospectively evaluated p53 alterations in 73 patients with locally advanced breast cancer (IIIB) submitted to neoadjuvant chemotherapy.
Patients and methods:
Patients received three cycles of paclitaxel (175 mg/m2) and doxorubicin (60 mg/m2) every 21 days. Tumor sections were analyzed before treatment for altered patterns of p53 expression using immunohistochemistry and DNA sequencing.
Results:
An overall response rate of 83.5% was obtained, including 15.1% complete pathological responses. The regimen was well tolerated with 17.7% grade 2/3 nausea and 12.8% grade 3/4 leukopenia. There was a statistically significant correlation between response and expression of p53. Of the 25 patients who obtained a complete clinical response, two were classified as positive (P = 0.004,
-square). Of 11 patients who obtained a complete pathological remission, one was positive (P = 0.099,
-square).
Discussion
The combination is highly effective in locally advanced breast cancer. A negative expression of p53 indicates a higher chance of responding to this regimen. The p53 status may be used as a biological marker to identify those patients who would benefit from more aggressive treatments.
Key words: breast cancer, doxorubicin, locally advanced, p53, paclitaxel
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