title: Pretreatment serum level of HER2/nue as a prognostic factor in metastatic prostate cancer patients about to undergo endocrine therapy.
abstract: BACKGROUND
  Overexpression of the HER2 receptor protein and amplification of the HER2 gene has been implicated in tumor development and progression, and has been associated with a poor prognosis in several types of cancer. The aim of this study was to evaluate whether pretreatment serum HER2 levels can be used to predict biochemical recurrence-free survival in prostate cancer patients about to undergo endocrine therapy.
  
  
  METHODS
  The study population consisted of 379 untreated patients with histologically diagnosed prostate cancer: 197 with T2N0M0, 93 with T3N0M0, 19 with TxN1Mx, and 70 with TxNxM1. Serum HER2 levels were assessed in the prostate cancer patients prior to treatment as well as in a control group of 100 patients with histologically confirmed non-cancer. Biochemical recurrence-free curves for the patients were investigated separately using the Kaplan-Meier method.
  
  
  RESULTS
  The mean level of HER2 in serum was significantly higher in prostate cancer patients than non-prostate cancer patients (P = 0.006). Also, the serum HER2 level was significantly higher in bone metastatic cancer patients (14.3 +/- 6.3 ng/mL) than in non-metastatic patients (T2: 11.9 +/- 2.3 ng/mL, P = 0.003; T3: 12.2 +/- 2.8 ng/mL, P = 0.011). The metastatic patients were divided into those with low and high HER2 levels using a cutoff value of 12.6 ng/mL based on receiver-operating characteristic curves. The biochemical recurrence-free rate was significantly poorer in patients with a high HER2 level (P = 0.0078, log-rank test). Multivariate Cox logistic regression analysis demonstrated that the pretreatment serum HER2 value (P = 0.022), serum prostate-specific antigen value (P = 0.018), and extent of disease score (P = 0.027) were independent predictors of recurrence.
  
  
  CONCLUSIONS
  The pretreatment serum HER2 level may be a useful independent prognostic factor that is associated with a high risk of biochemical recurrence in metastatic prostate cancer patients about to undergo endocrine therapy.
authors.affiliation: Department of Urology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan. toke@kyorin-u.ac.jp
authors.forename: Takatsugu
authors.initials: T
authors.lastname: Okegawa
authors.forename: Manami
authors.initials: M
authors.lastname: Kinjo
authors.forename: Kikuo
authors.initials: K
authors.lastname: Nutahara
authors.forename: Eiji
authors.initials: E
authors.lastname: Higashihara
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy / Q000556:secondary; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000813:Anilides / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D001859:Bone Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000556:secondary; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000097:blood*; D009367:Neoplasm Staging; D009570:Nitriles; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*; D012189:Retrospective Studies; D015996:Survival Rate; D014105:Tosyl Compounds; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D014408:Biomarkers, Tumor; D009570:Nitriles; D017430:Prostate-Specific Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D014105:Tosyl Compounds; C053541:bicalutamide