The Role of Genetic Variability in Drug Metabolism Pathways in Breast Cancer Prognosis

Pharmacogenomics. 2006 Jun;7(4):613-24. doi: 10.2217/14622416.7.4.613.

Abstract

Among patients receiving adjuvant therapy for breast cancer, there is variability in treatment outcomes, and it is unclear which patients will receive the most benefit from treatment and which will have better disease-free survival. To date, most studies of breast cancer prognosis have focused on tumor characteristics, but it is likely that pharmacogenetics, genetic variability in the metabolism of therapeutic agents, also plays a role in the prediction of survival. In this paper, we briefly discuss the metabolic pathways of drugs commonly used for the treatment of breast cancer (cyclophosphamide, doxorubicin, taxanes, tamoxifen and aromatase inhibitors) and describe the known genetic variants that may impact those pathways. Studies that have evaluated potential effects of these genetic variants on treatment outcomes are also discussed. It is likely that the application of pharmacogenetics, particularly in the setting of randomized clinical trials, will contribute to findings that may result in individualized therapeutic dosing.

Publication types

  • Review

MeSH terms

  • Anthracyclines / metabolism
  • Anthracyclines / therapeutic use
  • Antineoplastic Agents / metabolism*
  • Antineoplastic Agents / therapeutic use
  • Aromatase Inhibitors / metabolism
  • Aromatase Inhibitors / therapeutic use
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism*
  • Cyclophosphamide / metabolism
  • Cyclophosphamide / therapeutic use
  • Estrogen Receptor Modulators / metabolism
  • Estrogen Receptor Modulators / therapeutic use
  • Female
  • Genetic Variation
  • Humans
  • Pharmacogenetics
  • Prognosis
  • Taxoids / metabolism
  • Taxoids / therapeutic use

Substances

  • Anthracyclines
  • Antineoplastic Agents
  • Aromatase Inhibitors
  • Estrogen Receptor Modulators
  • Taxoids
  • Cyclophosphamide