17beta-Hydroxysteroid dehydrogenases involved in local oestrogen synthesis have prognostic significance in breast cancer

Br J Cancer. 2005 Feb 14;92(3):547-52. doi: 10.1038/sj.bjc.6602375.

Abstract

The 17beta-hydroxysteroid dehydrogenase (17HSD) enzymes are involved in the local regulation of sex steroids. The 17HSD type 1 enzyme catalyses the interconversion of the weak oestrone (E1) to the more potent oestradiol (E2), whereas 17HSD type 2 catalyses the oxidation of E2 to E1. The aim of this study was to correlate the expression of these enzymes in the tumour with the recurrence-free survival of tamoxifen-treated breast cancer patients. We used real-time reverse transcriptase PCR to investigate the mRNA expression of 17HSD types 1 and 2 in tumour samples from 230 postmenopausal patients. For the patients with oestrogen receptor (ER)-positive breast cancer, we found a statistically significant positive correlation between recurrence-free survival and expression of 17HSD type 2 (P=0.026). We examined the ratio of 17HSD types 2 and 1, and ER-positive patients with low ratios showed a significantly higher rate of recurrence than those with higher ratios (P=0.0047). ER positive patients with high expression levels of 17HSD type 1 had a significantly higher risk for late relapse (P=0.0051). The expression of 17HSD types 1 and 2 in breast cancer differs from the expression of these enzymes in normal mammary gland, and this study indicates that the expression has prognostic significance in breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 17-Hydroxysteroid Dehydrogenases / metabolism*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / enzymology*
  • Disease-Free Survival
  • Estrogens / metabolism
  • Female
  • Humans
  • Neoplasms, Hormone-Dependent / diet therapy
  • Neoplasms, Hormone-Dependent / enzymology
  • Prognosis
  • Tamoxifen / administration & dosage*
  • Time Factors

Substances

  • Estrogens
  • Tamoxifen
  • 17-Hydroxysteroid Dehydrogenases
  • 3 (or 17)-beta-hydroxysteroid dehydrogenase