Changes of topoisomerase IIalpha expression in breast tumors after neoadjuvant chemotherapy predicts relapse-free survival.
OBJECTIVE
To assess the value of changes in the expression of topoisomerase IIalpha (TopoII) and the proto-oncogene erbB-2 (HER-2) as predictors of relapse-free survival in women with operable breast cancer treated with anthracycline-based neoadjuvant chemotherapy.


METHODS
Seventy-seven patients with primary breast cancer who had undergone neoadjuvant anthracycline-based chemotherapy were included in the present study. TopoII and HER-2 were measured by immunohistochemistry in prechemotherapy and postchemotherapy (at the time of surgery) tumor specimens, and the value of their changes as predictors of relapse-free survival were evaluated by Kaplan-Meier and Cox proportional hazard regression analyses.


RESULTS
Neoadjuvant chemotherapy resulted in a significant reduction in the percentage of cells expressing TopoII (P < 0.0001). No significant change was observed for HER-2. TopoII and HER-2 expression before chemotherapy predicted tumor response to treatment. Changes in TopoII expression after chemotherapy were strongly associated with a poor relapse-free survival (P < 0.0001) in a Cox multivariate analysis adjusted for other clinicopathologic prognostic factors.


CONCLUSIONS
Changes in TopoII expression after anthracycline-based neoadjuvant chemotherapy is an independent predictor of a poor relapse-free survival in patients with breast cancer. Tumor cells displaying an increased TopoII expression after treatment may be responsible for relapses, and may, therefore, define a group of patients with anthracycline-resistant breast cancer.
Tinari
Nicola
N
G. D'Annunzio University Foundation and Department of Oncology and Neurosciences, University G. D'Annunzio Medical School, Chieti, Italy.
Lattanzio
Rossano
R
Natoli
Clara
C
Cianchetti
Ettore
E
Angelucci
Domenico
D
Ricevuto
Enrico
E
Ficorella
Corrado
C
Marchetti
Paolo
P
Alberti
Saverio
S
Piantelli
Mauro
M
Iacobelli
Stefano
S
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D003520:Cyclophosphamide / Q000627:therapeutic use; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D015251:Epirubicin / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008408:Mastectomy; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D018365:Neoplasm, Residual / Q000188:drug therapy / Q000378:metabolism; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D013237:Stereoisomerism
D000951:Antigens, Neoplasm; D003520:Cyclophosphamide; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D015251:Epirubicin; D005472:Fluorouracil; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases; C000715470:MAS1 protein, human