PPAR signaling pathway may be an important predictor of breast cancer response to neoadjuvant chemotherapy.
OBJECTIVE
Neoadjuvant chemotherapy for advanced breast cancer may improve the radicality for a subset of patients, but others may suffer from severe adverse drug reactions without any benefit. To predict the responses to chemotherapy, we performed a phase II trial of neoadjuvant chemotherapy using a weekly PCb [paclitaxel (Taxol) plus carboplatin] regimen for stage II/III breast cancer and assessed the correlation between baseline gene expression and the tumor response to treatment.


METHODS
A total of 61 patients with stage II-III breast cancer were included and administered four cycles of preoperative PCb. We performed a gene expression analysis using Affymetrix HG-U133 Plus 2.0 GeneChip arrays in 31 breast cancer tissues. Differentially expressed genes (DEGs) were identified by the significance analysis of microarrays (SAM) program using a false discovery rate of 0.05. The Functional Annotation Tool in the DAVID Bioinformatics Resources was used to perform the gene functional enrichment analysis. The other 30 patients (15 pCR and 15 non-pCR patients) were available as an independent validation set to test the selected DEGs by quantitative real-time PCR analysis (qRT-PCR).


RESULTS
By analyzing six pathological complete response (pCR) patients and 25 patients with non-pCR, 300 probes (231 genes) were identified as differentially expressed between pCR and residual disease by the SAM program when the fold change was >2. The gene functional enrichment analysis revealed 15 prominent gene categories that were different between pCR and non-pCR patients, most notably the genes involved in the peroxisome proliferator-activated receptor (PPAR), DNA repair and ER signal pathways and in the immune-related gene cluster. The qRT-PCR analysis results for the genes in the PPAR pathway (LPL, SORBS1, PLTP, SCD5, MMP1 and CSTA) in independent validation set were consistent with the results from the microarray data analysis.


CONCLUSIONS
In the present study, we identified a number of gene categories pertinent to the therapeutic response. We believe that the PPAR pathway may be an important predictor of genes that are involved in the chemotherapy response.
Department of Breast Surgery, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai, China.
Y Z
YZ
Chen
J Y
JY
Xue
C M
CM
Chen
B L
BL
Yang
Q H
QH
Xu
F
F
Wu
F
F
Liu
X
X
Ye
X
X
Meng
G Y
GY
Liu
Z Z
ZZ
Shen
Z M
ZM
Shao
J
J
Wu
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016190:Carboplatin / Q000008:administration & dosage; D004260:DNA Repair; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D017239:Paclitaxel / Q000008:administration & dosage; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D015398:Signal Transduction; D016896:Treatment Outcome
D047492:Peroxisome Proliferator-Activated Receptors; D016190:Carboplatin; D017239:Paclitaxel