Correlation of p53 status with outcome of neoadjuvant chemotherapy using paclitaxel and doxorubicin in stage IIIB breast cancer.
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.


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, chi-square). Of 11 patients who obtained a complete pathological remission, one was positive (P = 0.099, chi-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.
Anelli
A
A
Department of Medical Oncology, Hospital do Câncer de São Paulo, São Paulo, Brazil. aanelli@node1.com.br
Brentani
R R
RR
Gadelha
A P
AP
Amorim De Albuquerque
A
A
Soares
F
F
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D017239:Paclitaxel / Q000008:administration & dosage; D011237:Predictive Value of Tests; D011446:Prospective Studies; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; D017239:Paclitaxel