Multidrug resistance/P-glycoprotein and breast cancer: review and meta-analysis

Semin Oncol. 2005 Dec;32(6 Suppl 7):S9-15. doi: 10.1053/j.seminoncol.2005.09.009.

Abstract

Previously untreated breast cancer is relatively sensitive to a range of anticancer drugs. However, exposure to these drugs is often followed by acquisition of multidrug resistance, which is associated with a significantly worse outcome. One of the more widely studied mechanisms of drug resistance is the function of P-glycoprotein (P-gp), a membrane transporter with a wide range of substrates, including several anticancer agents, and a member of the ATP-binding cassette superfamily of proteins. A review of the published literature indicates that P-gp expression is detected in a significant percentage of breast cancers. Moreover, P-gp expression is increased after exposure to chemotherapeutic drugs (particularly those known to be P-gp substrates), and correlates with a worse response to treatment, especially when detected following treatment, in both the adjuvant and neoadjuvant settings. Consequently, P-gp represents a potential biomarker of drug resistance. However, a direct role of P-gp as a cause of clinical drug resistance has not been adequately tested in breast cancer. Future studies aimed at validating the mechanistic role of P-gp should include trials of multidrug resistance reversal using P-gp-specific inhibitors and relating results to the levels of P-gp expression. Future studies should also take into account the potentially multifactorial nature of multidrug resistance.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / chemistry
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology*
  • ATP-Binding Cassette Transporters / physiology
  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / therapy*
  • Drug Resistance, Multiple*
  • Drug Resistance, Neoplasm*
  • Humans

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP-Binding Cassette Transporters
  • Antineoplastic Agents