Serum HER2 extracellular domain predicts an aggressive clinical outcome and biological PSA response in hormone-independent prostate cancer patients treated with docetaxel

J. Domingo-Domenech, P. L. Fernandez, X. Filella, A. Martinez-Fernandez, R. Molina, E. Fernandez, A. Alcaraz, J. Codony, P. Gascon, B. Mellado*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

21 Citations (Scopus)

Abstract

Background: Human epidermal growth factor receptor 2 (HER2) overexpression has been linked to hormone-independent prostate cancer (HIPC) progression. Its clinical value and correlation with therapy is not defined.

Patients and methods: Patients with HIPC treated with docetaxel (Taxotere) were prospectively tested for serum HER2 extracellular domain (ECD) by immunoanalysis. HER2 was determined by immunohistochemistry and fluorescence in situ hybridization (FISH) in tumor samples.

Results: Sixty-nine patients were included. Twenty-four (34.8%) patients had high HER2 ECD (>1 5 ng/ml). Prostate-specific antigen (PSA) response was 58% for patients with low HER2 ECD and 36% for patients with high HER2 ECD (P = 0.046). HER2 ECD levels were an independent prognostic factor for time to PSA progression [hazard ratio (HR) 2.82; 95% confidence interval (CI) 1.22-6.50; P = 0.015] and overall survival (HR 3.24; 95% CI 1.38-7.59; P = 0.007). Tissue samples from 17 patients were tested for HER2. Patients with negative HER2 tissue expression had lower HER2 ECD levels (median 10.5 +/- 2.7 versus 30.5 +/- 24.8 ng/ml; P = 0.016). FISH was negative in all samples.

Conclusions: High HER2 ECD levels in serum are associated with a worst clinical outcome of HIPC patients treated with docetaxel.

Original languageEnglish
Pages (from-to)269-275
Number of pages7
JournalAnn. Oncol.
Volume19
Issue number2
DOIs
Publication statusPublished - Feb 2008

Keywords

  • docetaxel
  • HER2
  • HER2 ECD
  • hormone-independent prostate cancer
  • PHASE-II TRIAL
  • ANDROGEN-INDEPENDENCE
  • MOLECULAR ALTERATIONS
  • HER-2/NEU EXPRESSION
  • PROTEIN EXPRESSION
  • PROGRESSION
  • TRASTUZUMAB
  • GROWTH
  • BREAST
  • ESTRAMUSTINE

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