title: Predictive role of midtreatment changes in survivin, GSTP1, and topoisomerase 2α expressions for pathologic complete response to neoadjuvant chemotherapy in patients with locally advanced breast cancer.
abstract: BACKGROUND
  The primary aim of this study is to investigate the effect of change in the expression levels of survivin, glutathione-S-transferase P1 (GSTP1), and topoisomerase 2α (TOP2A) on the response to antracyclin-based and taxane-based neoadjuvant chemotherapy.
  
  
  METHODS
  This study included 32 locally advanced breast cancer patients. Tumoral expressions of survivin, TOP2A, and GSTP1 in serial biopsy specimens obtained before treatment, after sequential 4 cycles of doxorubicin+cyclophosphomide, and 4 cycles of docetaxel were analyzed by real-time polymerase chain reaction. Survivin expressions were additionally analyzed in serial blood samples.
  
  
  RESULTS
  The pathologic complete response (pCR) rate and the overall response rate (clinical complete and partial) were 28% (n=9) and 91% (n=29), respectively. There were no statistically significant correlations between serial TOP2A expression levels and response. There was a nonsignificant trend toward an improved response rate with decreased survivin expression. A significant decrease in the GSTP1 expression level throughout treatment (P=0.014), which was also shown to be significantly correlated with a pCR (P=0.0001), was seen. Downregulation of GSTP1 after 4 cycles of anthracycline-based combination was independently associated with improved progression-free survival (P=0.01).
  
  
  CONCLUSIONS
  Downregulation of GSTP1 is a significant predictor of pCR and improved progression-free survival during anthracycline-based and taxane-based neoadjuvant chemotherapy in patients with locally advanced breast cancer.
authors.affiliation: Department of Medical Oncology, Oncology Institute, Istanbul University, Istanbul, Turkey.
authors.forename: Yeşim
authors.initials: Y
authors.lastname: Eralp
authors.forename: Serkan
authors.initials: S
authors.lastname: Keskin
authors.forename: Ebru
authors.initials: E
authors.lastname: Akışık
authors.forename: Elif
authors.initials: E
authors.lastname: Akışık
authors.forename: Abdullah
authors.initials: A
authors.lastname: İğci
authors.forename: Mahmut
authors.initials: M
authors.lastname: Müslümanoğlu
authors.forename: Sabri
authors.initials: S
authors.lastname: Yılmaz
authors.forename: Mehtap
authors.initials: M
authors.lastname: Tunacı
authors.forename: Hakan
authors.initials: H
authors.lastname: Çamlıca
authors.forename: Sıtkı
authors.initials: S
authors.lastname: Tuzlalı
authors.forename: Pınar
authors.initials: P
authors.lastname: Saip
authors.forename: Nejat
authors.initials: N
authors.lastname: Dalay
authors.forename: Vahit
authors.initials: V
authors.lastname: Özmen
authors.forename: Erkan
authors.initials: E
authors.lastname: Topuz
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D003907:Dexamethasone / Q000008:administration & dosage; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D000075223:Poly-ADP-Ribose Binding Proteins; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D000077022:Survivin; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D000951:Antigens, Neoplasm; C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D051034:Inhibitor of Apoptosis Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D012333:RNA, Messenger; D000077022:Survivin; D043823:Taxoids; D000077143:Docetaxel; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human