title: Clinical significance of PTEN and p-Akt co-expression in HER2-positive metastatic breast cancer patients treated with trastuzumab-based therapies.
abstract: OBJECTIVE
  The phosphatase and tensine homologue gene (PTEN) plays a crucial role in proliferation and survival of cancer cells by antagonizing the function of phosphatidylinositol 3'-kinase (PI3K), which, in turn, results in decreased Akt activity. We investigated the clinical impact of the expression of PTEN, p-Akt and PI3K in HER2-positive metastatic breast cancer (MBC) patients treated with trastuzumab-based therapies.
  
  
  METHODS
  Seventy-three patients treated with trastuzumab-based therapies were included and followed prospectively. PTEN, p-Akt and PI3K expression was determined by immunohistochemistry.
  
  
  RESULTS
  PTEN, p-Akt and PI3K resulted positive in 48%, 71% and 46.5% of patients, respectively. A significant correlation between PTEN and p-Akt (kappa 0.22, p = 0.03) and p-Akt and PI3K (kappa 0.20, p = 0.05) was observed. PTEN-positive patients had a progression-free survival (PFS) longer than PTEN-negative ones (p = 0.06). When grouped together, patients co-expressing PTEN and p-Akt had a statistically significant longer PFS as compared to the rest of patients (p = 0.01). At the multivariate analysis, PTEN and p-Akt co-expression was an independent predictor of lower risk of progression (hazard ratio 0.53, p = 0.05).
  
  
  CONCLUSIONS
  In HER2-positive MBC, basal co-expression of PTEN and p-Akt might identify those patients who are more likely to benefit from trastuzumab-based therapies.
authors.affiliation: Division of Medical Oncology, Regina Elena Cancer Institute, Rome, Italy. alessandra.fabi@virgilio.it
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fabi
authors.forename: G
authors.initials: G
authors.lastname: Metro
authors.forename: A
authors.initials: A
authors.lastname: Di Benedetto
authors.forename: C
authors.initials: C
authors.lastname: Nisticò
authors.forename: P
authors.initials: P
authors.lastname: Vici
authors.forename: E
authors.initials: E
authors.lastname: Melucci
authors.forename: B
authors.initials: B
authors.lastname: Antoniani
authors.forename: L
authors.initials: L
authors.lastname: Perracchio
authors.forename: I
authors.initials: I
authors.lastname: Sperduti
authors.forename: M
authors.initials: M
authors.lastname: Milella
authors.forename: F
authors.initials: F
authors.lastname: Cognetti
authors.forename: M
authors.initials: M
authors.lastname: Mottolese
mesh_terms: D000293:Adolescent; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D051059:PTEN Phosphohydrolase; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human; C494929:PTEN protein, human