Predictive value of HER-2 and Topoisomerase IIalpha in response to primary doxorubicin in breast cancer.
OBJECTIVE
To study the predictive role of HER-2 and Topoisomerase IIalpha (TOP2A) in response to primary doxorubicin.


METHODS
Two hundred and thirty-two patients with operable breast cancer were treated with doxorubicin prior to surgery. ER, PgR, grade, Ki-67 and HER-2 status were prospectively assessed. HER-2 overexpression was evaluated with immunohistochemistry; positive cases were then studied for gene copy number of HER-2, TOP2A and chromosome 17 centromere by chromogenic in situ hybridisation. Clinical response was assessed by mammography. Pathological response was evaluated as the percentage of tumour replaced by changes due to chemotherapy.


RESULTS
HER-2 amplification was associated with clinical response (p=0.04). ER and PgR negativity, high Ki-67 and HER-2 amplification significantly correlated to pathological response (p<0.05). Tumours with coamplification of HER-2 and TOP2A showed a higher percentage of pathological changes (p=0.6). However, in the multivariate analysis for complete pathological response, ER negativity and high Ki-67 index were the only parameters that maintained statistical significance.


CONCLUSIONS
HER2 and Topoisomerase IIalpha amplification failed to show an association with pathological response to doxorubicin, whereas ER negativity and a high proliferation rate were predictive of complete pathological response to this regime.
Arriola
Edurne
E
Servicio de Oncologia Medica, Institut Catala d'Oncologia, Duran I Reynals, Hospitalet de Llobregat, Barcelona, Spain. edurne.arriola@icr.ac.uk
Moreno
Abelardo
A
Varela
Mar
M
Serra
Jose M
JM
Falo
Catalina
C
Benito
Enrique
E
Escobedo
Agustin P
AP
D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D002886:Chromosomes, Human, Pair 17 / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004317:Doxorubicin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D000075223:Poly-ADP-Ribose Binding Proteins; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D018709:Statistics, Nonparametric; D016615:Telomere / Q000378:metabolism; D016896:Treatment Outcome
D000903:Antibiotics, Antineoplastic; D000951:Antigens, Neoplasm; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D004317:Doxorubicin; D019394:Ki-67 Antigen; D000075223:Poly-ADP-Ribose Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C000618811:TOP2A protein, human