Aromatase in breast cancer and the role of aminoglutethimide and other aromatase inhibitors

Crit Rev Oncol Hematol. 1986;5(4):361-96. doi: 10.1016/s1040-8428(86)80003-8.

Abstract

Approximately one third of human breast carcinomas are hormone dependent and regress upon reduction of circulating estrogen levels. Traditional treatment strategies utilized surgical ablative methods to lower estrogen concentrations as treatment of breast cancer. Currently, investigative emphasis is focused upon development of highly specific antiestrogens and inhibitors of estrogen production. The enzyme, aromatase, as the terminal step in estrogen biosynthesis, is a logical target for blockade with potent and specific inhibitors. The earliest available aromatase antagonist, aminoglutethimide, suppresses estrogen production to the same extent as surgical ablation and is an effective treatment for breast cancer. Aminoglutethimide, however, blocks other cytochrome P-450-mediated steroid hydroxylations, requires concomitant glucocorticoid administration, and is associated with initial side effects. Several more specific inhibitors by destroying aromatase irreversibly as well as by competitive inhibition. One of these, 4-hydroxy-androstenedione, has been intensively studied in animals and is undergoing clinical trial. New data regarding these inhibitors further emphasize the key role of aromatase in estrogen production and the practical utility of blocking this enzyme.

Publication types

  • Clinical Trial
  • Comparative Study
  • Review

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene
  • Adult
  • Aged
  • Aminoglutethimide / adverse effects
  • Aminoglutethimide / pharmacology*
  • Aminoglutethimide / therapeutic use
  • Androgens / metabolism
  • Androstenedione / analogs & derivatives*
  • Androstenedione / pharmacology
  • Androstenedione / therapeutic use
  • Animals
  • Aromatase / metabolism
  • Aromatase / physiology
  • Aromatase Inhibitors*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / enzymology
  • Clinical Trials as Topic
  • Estrogens / biosynthesis
  • Estrogens / metabolism
  • Female
  • Humans
  • Mammary Neoplasms, Experimental / drug therapy
  • Mammary Neoplasms, Experimental / enzymology
  • Metabolic Clearance Rate
  • Middle Aged
  • Rats
  • Tamoxifen / pharmacology

Substances

  • Androgens
  • Aromatase Inhibitors
  • Estrogens
  • Tamoxifen
  • Aminoglutethimide
  • Androstenedione
  • 9,10-Dimethyl-1,2-benzanthracene
  • Aromatase
  • formestane