title: Lower level of MAPK expression is associated with anthracycline resistance and decreased survival in patients with hormone receptor negative breast cancer.
abstract: BACKGROUND
  Hormone receptor negative breast cancer is encountered in about 30% of all patients with breast cancer and is considered as a prognostically unfavorable subset. The aim of this study is to evaluate the prognostic impact of various molecular markers in patients with receptor negative breast cancer.
  
  
  METHODS
  Tumor specimens from 140 patients with receptor negative (ER, PR) breast cancer were analyzed for MAPK, Her-2/neu, EGFR and PI3K expression by immunohistochemistry. The prognostic significance of these molecular factors, in addition to various prognostic variables were determined with respect to disease-free and overall survival.
  
  
  RESULTS
  Nineteen (13.6%), 45 (32.1%), 16 (11.4%) and 47 (33.5%) patients had positive staining for EGFR, PI3K, Her-2/neu and MAPK, respectively. Twenty-three patients with positive MAPK (16.4%) had a high level of expression (score 4-7) and 24 (17.1%) had a low score (1-3). A lower percentage of MAPK expression was significantly associated with a poorer OS (p = 0.03) and a tendency for shorter DFS (p = 0.08) among those who were positive for MAPK. Anthracycline resistance remained the only independent significant variable for OS by Cox regression analysis (p = 0.001, HR:26.1). In patients with recurrent disease, median survival after initial relapse was 16.8 months. MAPK was determined as the only prognostic factor for this endpoint. Patients with higher level of MAPK staining showed significantly shorter survival following initial recurrence (p = 0.04).
  
  
  CONCLUSIONS
  MAPK expression is a significant prognostic factor for non-metastatic patients with hormone receptor breast cancer. A lower level of staining is shown to be associated with with antracycline resistance and oveall survival, whereas a higher expression level is correlated with shorter survival following initial relapse, suggesting possible role of different molecular mechanisms pertaining to tumor progression once recurrence occurs. Further translational research is required to elucidate molecular mechanisms of the cross-talk between intracellular signaling and molecular pathways leading to drug resistance in patients with receptor negative breast cancer.
authors.affiliation: Department of Medical Oncology, Institute of Oncology, Istanbul University.
authors.forename: Duygu
authors.initials: D
authors.lastname: Derin
authors.forename: Yesim
authors.initials: Y
authors.lastname: Eralp
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Ozluk
authors.forename: Ekrem
authors.initials: E
authors.lastname: Yavuz
authors.forename: Nese
authors.initials: N
authors.lastname: Guney
authors.forename: Pinar
authors.initials: P
authors.lastname: Saip
authors.forename: Abdullah
authors.initials: A
authors.lastname: Igci
authors.forename: Vahit
authors.initials: V
authors.lastname: Ozmen
authors.forename: Seden
authors.initials: S
authors.lastname: Kücücük
authors.forename: Isik
authors.initials: I
authors.lastname: Aslay
authors.forename: Adnan
authors.initials: A
authors.lastname: Aydiner
authors.forename: Erkan
authors.initials: E
authors.lastname: Topuz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality; D018572:Disease-Free Survival; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000032:analysis*; D019869:Phosphatidylinositol 3-Kinases / Q000032:analysis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis*; D017211:Treatment Failure
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C512478:EGFR protein, human; C508053:ERBB2 protein, human