Aromatase inhibitors and their application in breast cancer treatment*

Steroids. 2000 Apr;65(4):171-9. doi: 10.1016/s0039-128x(99)00104-x.

Abstract

Estrogens are known to be important in the growth of breast cancers in both pre- and postmenopausal women. The number of breast cancer patients with hormone-dependent disease increases with age, as does the incidence of breast cancer. Although estrogens are no longer made in the ovaries after menopause, peripheral tissues produce sufficient concentrations to stimulate tumor growth. Because aromatase catalyzes the rate-limiting step in the biosynthesis of estrogen, inhibitors of this enzyme have been developed in the last few years as a logical treatment strategy. Two classes of aromatase inhibitors, steroidal and nonsteroidal compounds, are now in use. Among the steroid substrate analogs, formestane and examestane have been shown to be effective in breast cancer patients with advanced disease. Highly potent and selective nonsteroidal inhibitors have recently been found to suppress plasma and urinary estrogens by more than 95% in breast cancer patients. Two of these compounds recently were approved in the United States and have been shown to be more effective than other second-line agents in terms of overall response rates and treatment failure, as well as better tolerated. Although studies of the efficacy of these agents in earlier stage disease are awaited, it is evident that aromatase inhibitors can extend the duration of treatment in breast cancer patients.

Publication types

  • Review

MeSH terms

  • Androstenedione / analogs & derivatives
  • Androstenedione / pharmacology
  • Androstenedione / therapeutic use
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Aromatase / genetics
  • Aromatase / metabolism
  • Aromatase Inhibitors*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use*
  • Estrogens / metabolism
  • Female
  • Humans
  • Letrozole
  • Mice
  • Nitriles / pharmacology
  • Nitriles / therapeutic use
  • Tamoxifen / therapeutic use
  • Triazoles / pharmacology
  • Triazoles / therapeutic use

Substances

  • Antineoplastic Agents
  • Aromatase Inhibitors
  • Enzyme Inhibitors
  • Estrogens
  • Nitriles
  • Triazoles
  • Tamoxifen
  • Androstenedione
  • Letrozole
  • Aromatase
  • formestane