DNA topoisomerase IIalpha expression and the response toprimary chemotherapy in breast cancer.
The alpha isoform of Topoisomerase IIalpha (Topo IIalpha) is a proliferation marker as well as a target for several chemotherapeutic agents such as anthracyclines. In vitro studies have demonstrated the relationship between the Topo IIalpha expression level and chemosensitivity of target cancer cells. To verify this effect in vivo, we selected 125 patients presenting with T(2)>3 cm and T(3) N(0-1) M(0) breast tumours who were treated by six cycles of primary chemotherapy, including epirubicin before any surgery. Therapy response was assessed by clinical and X-ray mammogram measurements of tumour shrinkage. The pretherapeutic core biopsies were immunostained with a monoclonal antibody (Ki-S7) against Topo IIalpha. Ki-S7 positivity ranged from 0 to 50% (median, 15%). A high percentage of Ki-S7-positive cells (>15%) was associated with tumour regression under chemotherapy (OR=2.88, CI: 1.3-6.4, P=0.004). Ki-S7 further emerged as an independent predictor of tumour regression (OR=3.34, CI: 1.41-7.93, P=0.006), together with tumour size of less than 40 mm (OR=3.82, CI: 1.58-9.25, P=0.002) and negative oestrogen receptor (ER) status (OR=3.35, CI: 1.43-7.86, P=0.005), in a multivariate analysis including tumour size, SBR grade, ER and PR status, Ki-67, p53 and Her-2/neu. Our clinical results confirm in vitro data on the relationship between Topo IIalpha expression and tumour chemosensitivity and thus may have important practical implications.
MacGrogan
G
G
Department of Pathology, Institut Bergonié, 229 Cours de l'Argonne, 33076 Bordeaux cedex France. macgrogan@bergonie.org
Rudolph
P
P
Mascarel Id
I de
Id
Mauriac
L
L
Durand
M
M
Avril
A
A
Dilhuydy
J M
JM
Robert
J
J
Mathoulin-Pélissier
S
S
Picot
V
V
Floquet
A
A
Sierankowski
G
G
Coindre
J M
JM
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins; D018450:Disease Progression; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008327:Mammography; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011237:Predictive Value of Tests; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D014057:Tomography, X-Ray Computed; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53