title: Tumour topoisomerase II alpha protein expression and outcome after adjuvant dose-dense anthracycline-based chemotherapy.
abstract: There is a need for the selection of those breast cancers where benefit may be attained from the addition of an anthracycline to the adjuvant chemotherapy. The expression of topoisomerase II alpha (TOP2A) protein in 3 cohorts of breast cancers treated with adjuvant dose-dense anthracycline-based chemotherapy was determined retrospectively. The TOP2A status was analysed in relation with the other standard tumour features and the outcome. TOP2A IHC results were assessable in 106 patients: with a cut-off value of 15%, 48% of the tumours were classified as TOP2A-positive. The expression of TOP2A correlated with that of Ki67 (R = 0.532, p < 0.001) and a high grade (p = 0.04), but did not correlate with the proportion of ER- or PR-positive cells in the tumour. More tumors were TOP2A-negative among the ER- or PR-positive cancers than among the ER/PR-negative cancers (p = 0.021 and p = 0.002, respectively). After a median follow-up time of 64.5 months, 31 relapses (23.5%) and 23 deaths (17.4%) had occurred in 131 patients. The overall survival was longer in the TOP2A-positive cases than in the TOP2A-negative cases. The recurrence-free survival and the overall survival were significantly more favourable in the ER/PR-negative and TOP2A-positive tumours than in other subgroups. In a Cox proportional hazards model, the grade and TOP2A remained significant determinants in the ER/PR-negative subgroup. TOP2A positivity and grade 3 indicated a decrease in the risk of death with HR = 0.211 (95% CI: 0.042-1.05, p = 0.056) and HR = 0.216 (95% CI: 0.047-0.990, p = 0.048), respectively. A higher sensitivity to anthracycline-containing regimens is suggested in ER/PR-negative and TOP2A-positive cancers.
authors.affiliation: Department of Oncotherapy, University of Szeged, Hungary.
authors.forename: Alíz
authors.initials: A
authors.lastname: Nikolényi
authors.forename: Gabriella
authors.initials: G
authors.lastname: Uhercsák
authors.forename: Melinda
authors.initials: M
authors.lastname: Csenki
authors.forename: Sándor
authors.initials: S
authors.lastname: Hamar
authors.forename: Erika
authors.initials: E
authors.lastname: Csörgo
authors.forename: Ervin
authors.initials: E
authors.lastname: Tánczos
authors.forename: László
authors.initials: L
authors.lastname: Thurzó
authors.forename: Thomas
authors.initials: T
authors.lastname: Brodowicz
authors.forename: Maria
authors.initials: M
authors.lastname: Wagnerova
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Kahán
mesh_terms: D000704:Analysis of Variance; D018943:Anthracyclines / Q000008:administration & dosage; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D000075223:Poly-ADP-Ribose Binding Proteins; D016016:Proportional Hazards Models; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D000075223:Poly-ADP-Ribose Binding Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human