title: The Predictive and Prognostic Role of Topoisomerase IIα and Tissue Inhibitor of Metalloproteinases 1 Expression in Locally Advanced Breast Carcinoma of Egyptian Patients Treated With Anthracycline-based Neoadjuvant Chemotherapy.
abstract: OBJECTIVE
  Locally advanced breast cancer (LABC) is a heterogeneous entity that remains a clinical challenge. Anthracycline-based neoadjuvant chemotherapy has emerged as the standard of care for those patients. However, it is associated with serious side effects including cardiotoxicity. This study aimed to evaluate the prognostic and predictive role of topoisomerase IIα (TOP2α) and tissue inhibitor of metalloproteinases 1 (TIMP-1) in Egyptian LABC patients after anthracycline-based neoadjuvant chemotherapy.
  
  
  METHODS
  This retrospective study was conducted on 84 LABC cases. Immunohistochemical expression of TOP2α and TIMP-1 was evaluated in pretreatment needle core biopsies. Results were correlated with clinicopathlogic parameters, response to neoadjuvant chemotherapy in postoperative specimens, disease-free survival and overall survival (OS).
  
  
  RESULTS
  Positive TOP2α expression was detected in 57/84 (67.9%) cases. It was significantly associated with good response to chemotherapy in breast (P=0.048) and lymph node (P=0.06) as well as prolonged OS (P=0.04). It tended to be the most independent prognostic factor for OS (P=0.06). Positive TIMP-1 expression was detected in 48/84 (57.1%) cases. It was significantly associated with poor response to chemotherapy in breast (P=0.02). The 2T profile (TOP2α+ and TIMP-1-) was significantly associated with good response to chemotherapy in breast (P=0.006).
  
  
  CONCLUSIONS
  TOP2α and TIMP-1 are important predictive and prognostic factors in LABC patients who received anthracycline-based chemotherapy.
authors.affiliation: *Pathology Department, Faculty of Medicine, Menofia University, Shebin El Kom †Pathology Department ‡Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
authors.forename: Hala S
authors.initials: HS
authors.lastname: El Rebey
authors.forename: Hayam A S
authors.initials: HA
authors.lastname: Aiad
authors.forename: Iman L
authors.initials: IL
authors.lastname: Abulkheir
authors.forename: Nancy Y
authors.initials: NY
authors.lastname: Asaad
authors.forename: Moshira M A
authors.initials: MM
authors.lastname: El-Wahed
authors.forename: Fatma M
authors.initials: FM
authors.lastname: Abulkasem
authors.forename: Shereen F
authors.initials: SF
authors.lastname: Mahmoud
mesh_terms: D018943:Anthracyclines / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004534:Egypt; D005260:Female; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D018943:Anthracyclines; D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D004250:DNA Topoisomerases, Type II