P-glycoprotein: the intermediate end point of drug response to induction chemotherapy in locally advanced breast cancer

Breast Cancer Res Treat. 1997 Jan;42(1):65-72. doi: 10.1023/a:1005739525196.

Abstract

Expression and clinical relevance of p-glycoprotein (p-gp) were evaluated in 31 cases of locally advanced breast cancer and 9 cases involving inflammatory breast cancer after induction chemotherapy. The de novo p-gp expression rate was 26% and increased up to 58% (p = 0.03) with the FAC (5-fluorouracil, adriamycin, cyclophosphamide) regimen. Although more clinically complete responders were found in the secondary p-gp negative group (p = 0.02), this difference was not found in pathological tumor response. Moreover, as the grade of the secondary p-gp expression increased, the chemotherapeutic effect decreased, suggesting an inverse relationship between p-gp expression and drug effect (p = 0.04). When we subgrouped the patients into 4 groups using these two parameters, p-gp negative patients presenting with a high drug effect showed a low recurrence rate (p = 0.05) and marginal survival benefits (p = 0.09) as opposed to patients with a low drug effect. But in p-gp positive groups, the recurrence rate was the same between the two groups regardless of the drug effect. Thus, in the p-gp negative patient with a high drug effect, adjuvant chemotherapy with the same regimen as induction chemotherapy may induce more prognostically favorable results. Therefore, clinical application of the secondary p-gp detection can be used as an intermediate endpoint in evaluating drug response for an induction regimen.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis*
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / drug therapy*
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / pathology
  • Chemotherapy, Adjuvant
  • Cyclophosphamide / administration & dosage
  • Doxorubicin / administration & dosage
  • Drug Resistance, Multiple*
  • Drug Resistance, Neoplasm
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Doxorubicin
  • Cyclophosphamide
  • Fluorouracil

Supplementary concepts

  • CAF protocol