Prediction of docetaxel response in human breast cancer by gene expression profiling.
OBJECTIVE
Docetaxel is one of the most effective anticancer drugs available in the treatment of breast cancer. Nearly half of the treated patients, however, do not respond to chemotherapy and suffer from side effects. The ability to reliably predict a patient's response based on tumor gene expression will improve therapeutic decision making and save patients from unnecessary side effects.


METHODS
A total of 44 breast tumor tissues were sampled by biopsy before treatment with docetaxel, and the response to therapy was clinically evaluated by the degree of reduction in tumor size. Gene expression profiling of the biopsy samples was performed with 2,453 genes using a high-throughput reverse transcriptase polymerase chain reaction technique. Using genes differentially expressed between responders and nonresponders, a diagnostic system based on the weighted-voting algorithm was constructed.


RESULTS
This system predicted the clinical response of 26 previously unanalyzed samples with over 80% accuracy, a level promising for clinical applications. Diagnostic profiles in nonresponders were characterized by elevated expression of genes controlling the cellular redox environment (ie, redox genes, such as thioredoxin, glutathione-S-transferase, and peroxiredoxin). Overexpression of these genes protected cultured mammary tumor cells from docetaxel-induced cell death, suggesting that enhancement of the redox system plays a major role in docetaxel resistance.


CONCLUSIONS
These results suggest that the clinical response to docetaxel can be predicted by gene expression patterns in biopsy samples. The results also suggest that one of the molecular mechanisms of the resistance is activation of a group of redox genes.
Iwao-Koizumi
Kyoko
K
Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-2 Nakamichi, Higashinari-ku, Osaka 537-8511, Japan.
Matoba
Ryo
R
Ueno
Noriko
N
Kim
Seung Jin
SJ
Ando
Akiko
A
Miyoshi
Yasuo
Y
Maeda
Eisaku
E
Noguchi
Shinzaburo
S
Kato
Kikuya
K
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D001706:Biopsy; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis; D003657:Decision Making; D000077143:Docetaxel; D005260:Female; D005544:Forecasting; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D043823:Taxoids / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D043823:Taxoids; D000077143:Docetaxel