Topoisomerase-II alpha expression as a predictive marker in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin or single-agent docetaxel.
OBJECTIVE
The predictive value of topoisomerase-II alpha (topo-II) has been evaluated in advanced breast cancer patients randomly treated with single-agent doxorubicin or docetaxel.


METHODS
Primary tumor samples from patients enrolled in a randomized, phase III clinical trial comparing single-agent doxorubicin (75 mg/m(2) q3wks) with docetaxel (100 mg/m(2) q3wks) were collected and topo-II status was evaluated by immunohistochemistry (clone KiS1).


RESULTS
Topo-II status was evaluated in 108 samples, 55 (51%) in the doxorubicin arm and 53 (49%) in the docetaxel arm. An increment of 10% in cells expressing topo-II is associated with a statistically significant odds ratio (OR; 95% confidence interval) of 1.09 (1.03-1.15; P = 0.002) for overall response to doxorubicin versus 1.002 (0.94-1.07; P = 0.95) in the docetaxel arm. With increasing topo-II, the favorable OR for overall response to docetaxel compared with doxorubicin decreases to become not significant in patients with topo-II tumor content >10%. In a multivariate analysis, (a) HER-2 status seems positively correlated with overall response to chemotherapy (OR, 2.34; 95% confidence interval, 0.87-6.27; P = 0.09). (b) Overall response to doxorubicin is significantly lower than overall response to docetaxel (OR, 0.17; 95% confidence interval, 0.04-0.64; P = 0.009) but with a significant interaction term for doxorubicin-treated patients with topo-II tumor content >10% (OR, 8.31; 95% confidence interval, 1.86-37.03; P = 0.05).


CONCLUSIONS
(a) Topo-II overexpression confers a higher probability of response in the doxorubicin arm only. (b) Despite being a small retrospective study, this study is in line with previously reported studies and the hypotheses raised are now being tested in a prospective neoadjuvant trial.
Jules Bordet Institute, 125 Boulevard de Waterloo, 1000 Brussels, Belgium.
Virginie
V
Durbecq
Marianne
M
Paesmans
Fatima
F
Cardoso
Christine
C
Desmedt
Angelo
A
Di Leo
Stephen
S
Chan
Kay
K
Friedrichs
Tamas
T
Pinter
Simon
S
Van Belle
Elizabeth
E
Murray
István
I
Bodrogi
Euan
E
Walpole
Bernard
B
Lesperance
Stefan
S
Korec
John
J
Crown
Peter
P
Simmonds
Thimothy J
TJ
Perren
Jean-Yves
JY
Leroy
Ghizlane
G
Rouas
Christos
C
Sotiriou
Martine
M
Piccart
Denis
D
Larsimont
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D045744:Cell Line, Tumor; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis* / Q000235:genetics*; D004268:DNA-Binding Proteins; D000077143:Docetaxel; D004317:Doxorubicin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D000075223:Poly-ADP-Ribose Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012189:Retrospective Studies; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D000077143:Docetaxel; D004317:Doxorubicin; D000075223:Poly-ADP-Ribose Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; C000618811:TOP2A protein, human