Multidrug resistance in locally advanced breast cancer

Tumour Biol. 2006;27(6):309-18. doi: 10.1159/000096086. Epub 2006 Oct 9.

Abstract

Background: Advanced breast cancer cases can still be encountered resulting in poor prognosis. The primary treatment for these patients is chemotherapy, and multidrug resistance (MDR) is a serious obstacle in the treatment. Detecting drug resistance before first-line chemotherapy may increase the patient's survival. In this study, the role of MDR is evaluated in locally advanced breast cancer patients.

Methods: Reverse transcriptase polymerase chain reaction was used for the detection of MDR genes, ABCB1 and ABCC1. Immunohistochemistry was used for the detection of MDR proteins, P-glycoprotein (Pgp) and MDR-associated protein 1.

Results: Breast tissues from 25 patients both before and after chemotherapy were examined. Five patients were unresponsive to chemotherapy. Four had ABCB1 gene expression induced by chemotherapy, and Pgp positivity was detected in 9 patients after chemotherapy. Both the induction of ABCB1 gene expression (p < 0.001) and Pgp positivity (p < 0.001) during chemotherapy were significantly related with clinical response. Although 80% of the clinically unresponsive patients had ABCC1 gene expression, the relation between ABCC1 expression and clinical drug response was not significant.

Conclusion: In locally advanced breast cancer, ABCB1 gene expression during chemotherapy contributes to clinical unresponsiveness. However, ABCC1 gene expression did not correlate strongly with the clinical response.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • DNA Primers
  • DNA, Complementary / genetics
  • Drug Resistance, Multiple*
  • Female
  • Humans
  • Lymphatic Metastasis
  • Multidrug Resistance-Associated Proteins / genetics*
  • Organic Anion Transporters / genetics*
  • Polymerase Chain Reaction
  • Prognosis
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • DNA Primers
  • DNA, Complementary
  • Multidrug Resistance-Associated Proteins
  • Organic Anion Transporters
  • multidrug resistance-associated protein 1