Global gene expression changes during neoadjuvant chemotherapy for human breast cancer.
OBJECTIVE
The purpose of this study was to analyze global gene expression changes in serial tumor core biopsy specimens taken during neoadjuvant chemotherapy for primary breast cancer.


METHODS
Core biopsy specimens from tumors were obtained before treatment and 24 and/or 48 hours after treatment from 21 women who were beginning chemotherapy for breast cancer. RNA was extracted, and radiolabeled complementary DNA was synthesized. The complementary DNA probes were hybridized to high-density microarray membranes that contained more than 25,000 human sequence clones. Hierarchical cluster analysis was used to compare the degree of similarity between expression profiles.


RESULTS
Twenty-five (45%) of the 56 available core specimens yielded sufficient quantity and quality RNA for microarray analysis. Microarray profiles were performed only on samples from patients with pretreatment and posttreatment specimens, resulting in serial data sets for five patients (14 specimens). The serial samples from individual patients clustered more closely than the samples taken from different patients. Analyses of the variance of individual gene expression showed that there were significantly fewer genes with fivefold differences in expression in an individual tumor at different times (average, 359 genes) versus pretreatment samples of different tumors (average, 732 genes). Patients with a good pathological response to treatment had gene patterns that clustered distinctly from those of poor responders. Significant transcriptional response occurred in all patients during therapy. Surprisingly, all patients had different genes change after chemotherapy, with no single gene having a significant expression change in all five patients.


CONCLUSIONS
This is the first report to show global gene expression changes during chemotherapy in a human solid tumor. Comprehensive gene expression profiles of more than 25,000 genes can be obtained from core biopsy specimens. A remarkable diversity in transcriptional response was observed for individual cases. Further data are needed to determine whether gene profiling can predict response to chemotherapy.
Buchholz
Thomas A
TA
Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Stivers
David N
DN
Stec
James
J
Ayers
Mark
M
Clark
Edward
E
Bolt
Andrew
A
Sahin
Aysegul A
AA
Symmans
W Fraser
WF
Hess
Kenneth R
KR
Kuerer
Henry M
HM
Valero
Vicente
V
Hortobagyi
Gabriel N
GN
Pusztai
Lajos
L
D000704:Analysis of Variance; D001706:Biopsy / Q000379:methods; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D016000:Cluster Analysis; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020360:Neoadjuvant Therapy; D020411:Oligonucleotide Array Sequence Analysis; D010865:Pilot Projects; D012334:RNA, Neoplasm / Q000032:analysis; D012044:Regression Analysis; D015203:Reproducibility of Results
D012334:RNA, Neoplasm