title: HER-2 profiling and targeting in prostate carcinoma.
abstract: BACKGROUND
  The clinical effects of targeting HER-2 in prostate carcinoma are not known. This study explored the feasibility of molecular profiling to determine the correlation between HER-2 expression, hormonal sensitivity, and the antitumor effects of trastuzumab and paclitaxel in patients with prostate carcinoma.
  
  
  METHODS
  Patients with progressive androgen dependent (AD) and androgen independent (AI) prostate carcinoma were eligible to participate in the study. HER-2 expression was assessed on pretreatment tissue specimens, and patients were then assigned to one of four treatment groups: AD HER-2 positive, AD HER-2 negative, AI HER-2 positive, and AI HER-2 negative. They were treated with weekly trastuzumab at a dose of 2 mg/kg (after a 4 mg/kg loading dose) until they experienced disease progression, when weekly paclitaxel at 100 mg/m(2) was added.
  
  
  RESULTS
  The authors screened 130 patients for HER-2 expression. In total, 23 patients were treated. Six eligible patients had HER-2 positive disease; therefore, only the AI HER-2 negative arm accrued to completion. All patients (100%) experienced disease progression on trastuzumab alone at or before the first 12 weeks of treatment. Fifteen patients received combined therapy: Seven patients (47%) experienced disease progression, 5 patients (33%) had stable disease, and 3 patients (20%) had a decline > or = 50% in prostate specific antigen PSA level or in soft tissue disease. HER-2 overexpression was found in significant proportions only in AI metastatic tissue samples (42% HER-2 positive; 95% confidence interval, 14-60%). In three of nine matched pairs, the AD prostate biopsy was HER-2 negative, and the AI metastatic sample was HER-2 positive.
  
  
  CONCLUSIONS
  Trastuzumab is not effective as a single agent for the treatment of patients with AI HER-2 negative tumors. HER-2 expression varies by clinical state in patients with prostate carcinoma: Accurate HER-2 profiling requires sampling metastatic tissue in patients with metastatic disease. Further development of trastuzumab for the treatment of patients with metastatic prostate carcinoma is not feasible until more reliable and practical methods of sampling metastatic disease are developed to identify patients with HER-2 positive tumors.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Morris
authors.forename: Victor E
authors.initials: VE
authors.lastname: Reuter
authors.forename: W Kevin
authors.initials: WK
authors.lastname: Kelly
authors.forename: Susan F
authors.initials: SF
authors.lastname: Slovin
authors.forename: Kate
authors.initials: K
authors.lastname: Kenneson
authors.forename: David
authors.initials: D
authors.lastname: Verbel
authors.forename: Iman
authors.initials: I
authors.lastname: Osman
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel; D017430:Prostate-Specific Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab