title: Tumor topoisomerase II alpha status and response to anthracycline-based neoadjuvant chemotherapy in breast cancer.
abstract: OBJECTIVE
  Individualized chemotherapy for breast cancer improves the outcome. Anthracyclines target the enzyme topoisomerase IIα (TOP2A). We set out to perform a retrospective study of the presence of gene abnormalities and the expression of TOP2A in a cohort of breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy.
  
  
  METHODS
  Forty-three patients with 45 breast cancers were treated with neoadjuvant docetaxel-epirubicin with/without capecitabine chemotherapy. The TOP2A status of the cancers, determined retrospectively by fluorescent in situ hybridization and immunohistochemistry, was analyzed in relation to the standard clinical and pathological data.
  
  
  RESULTS
  Clinically and pathologically complete remission (pCR) was achieved in 15 (33.3%) and 9 (20%) cases, respectively. The TOP2A gene was amplified in 2 human epidermal growth factor receptor 2 (HER2)-positive cancers (8%), and 32 (84.2%) overall exhibited TOP2A expression in >15% of the cells. The expression of TOP2A exhibited a strong correlation with the expression of Ki67 (R = 0.743, p < 0.001), and was negatively correlated with estrogen receptors (ER; R = 0.404, p = 0.012) and progesterone receptors (R = 0.430, p = 0.007). The expression of TOP2A was not related to the amplification of the TOP2A gene or the HER2 status of the tumor. The proportions of Ki67- and TOP2A-positive tumor cells were significantly reduced after chemotherapy (56.1 ± 23.6 vs. 19.0 ± 27.7%, p = 0.004, and 41.0 ± 27.9 vs. 12.7 ± 24.8%, p < 0.001, respectively). The development of pCR was related to a high grade (p = 0.054), ER negativity (p = 0.027) and high TOP2A expression (p = 0.037). The expression of TOP2A was an independent predictor of pCR (OR = 1.460, for every 10% increase, 95% CI: 1.016-2.096, p = 0.041). After a median follow-up time of 31.0 months, neither relapse-free survival nor overall survival was related to the tumor response.
  
  
  CONCLUSIONS
  TOP2A expression is a marker of the tumor's proliferation rate and sensitivity to anthracycline-based chemotherapy, and does not depend on the amplification of its gene.
authors: Department of Oncotherapy, University of Szeged, Szeged, Hungary.
authors: Alíz
authors: A
authors: Nikolényi
authors: Farkas
authors: F
authors: Sükösd
authors: László
authors: L
authors: Kaizer
authors: Erika
authors: E
authors: Csörgo
authors: András
authors: A
authors: Vörös
authors: Gabriella
authors: G
authors: Uhercsák
authors: Katalin
authors: K
authors: Ormándi
authors: György
authors: G
authors: Lázár
authors: László
authors: L
authors: Thurzó
authors: Thomas
authors: T
authors: Brodowicz
authors: Zsuzsanna
authors: Z
authors: Kahán
mesh_terms: D000328:Adult; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D000069287:Capecitabine; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D018275:Carcinoma, Lobular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D000077143:Docetaxel; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D015870:Gene Expression; D018734:Genes, erbB-2 / Q000235:genetics; D006801:Humans; D007120:Immunochemistry; D017404:In Situ Hybridization, Fluorescence; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D000075223:Poly-ADP-Ribose Binding Proteins; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D000075223:Poly-ADP-Ribose Binding Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D015251:Epirubicin; D000069287:Capecitabine; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human; D005472:Fluorouracil