Gene expression patterns in formalin-fixed, paraffin-embedded core biopsies predict docetaxel chemosensitivity in breast cancer patients.
Previously, we had identified gene expression patterns that predicted response to neoadjuvant docetaxel. Other studies have validated that a high Recurrence Score (RS) by the 21-gene RT-PCR assay is predictive of worse prognosis but better response to chemotherapy. We investigated whether tumor expression of these 21 genes and other candidate genes can predict response to docetaxel. Core biopsies from 97 patients were obtained before treatment with neoadjuvant docetaxel (4 cycles, 100 mg/m2 q3 weeks). Three 10-microm FFPE sections were submitted for quantitative RT-PCR assays of 192 genes that were selected from our previous work and the literature. Of the 97 patients, 81 (84%) had sufficient invasive cancer, 80 (82%) had sufficient RNA for QRTPCR assay, and 72 (74%) had clinical response data. Mean age was 48.5 years, and the median tumor size was 6 cm. Clinical complete responses (CR) were observed in 12 (17%), partial responses in 41 (57%), stable disease in 17 (24%), and progressive disease in 2 patients (3%). A significant relationship (P<0.05) between gene expression and CR was observed for 14 genes, including CYBA. CR was associated with lower expression of the ER gene group and higher expression of the proliferation gene group from the 21 gene assay. Of note, CR was more likely with a high RS (P=0.008). We have established molecular profiles of sensitivity to docetaxel. RT-PCR technology provides a potential platform for a predictive test of docetaxel chemosensitivity using small amounts of routinely processed material.
Chang
Jenny C
JC
Breast Center and the Department of Medicine, Baylor College of Medicine and the Methodist Hospital, 1 Baylor Plaza, MS 600, Houston, TX 77030, USA. jcchang@bcm.edu
Makris
Andreas
A
Gutierrez
M Carolina
MC
Hilsenbeck
Susan G
SG
Hackett
James R
JR
Jeong
Jennie
J
Liu
Mei-Lan
ML
Baker
Joffre
J
Clark-Langone
Kim
K
Baehner
Frederick L
FL
Sexton
Krsytal
K
Mohsin
Syed
S
Gray
Tara
T
Alvarez
Laura
L
Chamness
Gary C
GC
Osborne
C Kent
CK
Shak
Steven
S
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001706:Biopsy; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D000077143:Docetaxel; D005260:Female; D005404:Fixatives; D005557:Formaldehyde; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D005820:Genetic Testing; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D016612:Paraffin Embedding; D018579:Patient Selection; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000235:genetics; D011960:Receptors, Estrogen / Q000032:analysis / Q000235:genetics; D011980:Receptors, Progesterone / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043823:Taxoids / Q000627:therapeutic use*; D016707:Tissue Fixation / Q000379:methods*; D016896:Treatment Outcome; D006113:United Kingdom; D014481:United States
D000970:Antineoplastic Agents; D000077143:Docetaxel; D005404:Fixatives; D005557:Formaldehyde; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D043823:Taxoids; C508053:ERBB2 protein, human