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

Am J Clin Oncol. 2013 Jun;36(3):215-23. doi: 10.1097/COC.0b013e318243913f.


Introduction: 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.

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm / genetics*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / genetics
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Cyclophosphamide / administration & dosage
  • DNA Topoisomerases, Type II / genetics*
  • DNA-Binding Proteins / genetics*
  • Dexamethasone / administration & dosage
  • Docetaxel
  • Doxorubicin / administration & dosage
  • Female
  • Follow-Up Studies
  • Glutathione S-Transferase pi / genetics*
  • Humans
  • Inhibitor of Apoptosis Proteins / genetics*
  • Middle Aged
  • Neoadjuvant Therapy*
  • Neoplasm Staging
  • Poly-ADP-Ribose Binding Proteins
  • Prognosis
  • Prospective Studies
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Remission Induction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate
  • Survivin
  • Taxoids / administration & dosage


  • Antigens, Neoplasm
  • BIRC5 protein, human
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Inhibitor of Apoptosis Proteins
  • Poly-ADP-Ribose Binding Proteins
  • RNA, Messenger
  • Survivin
  • Taxoids
  • Docetaxel
  • Dexamethasone
  • Doxorubicin
  • Cyclophosphamide
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • DNA Topoisomerases, Type II
  • TOP2A protein, human