title: Clinical role of multidrug resistance protein 1 expression in chemotherapy resistance in early-stage breast cancer: the Austrian Breast and Colorectal Cancer Study Group.
abstract: OBJECTIVE
  The multidrug resistance protein 1 (MRP1) is expressed in human breast cancer cells and may contribute to the clinical drug resistance of breast cancer patients. Therefore, we determined the impact of MRP1 expression on the clinical outcome of adjuvant therapy in patients with early-stage breast cancer.
  
  
  METHODS
  Immunostaining for MRP1 was performed on tissue sections from 516 premenopausal, hormone receptor-positive breast cancer patients with stage I and II disease. Statistical analyses were performed to assess the effect of MRP1 expression on survival and to test for interaction between MRP1 expression and treatment.
  
  
  RESULTS
  MRP1 expression independently predicted shorter relapse-free survival (RFS) and overall survival (OS) in patients treated with cyclophosphamide, methotrexate, and fluorouracil (CMF; RFS: hazard ratio [HR] = 1.48; 95% CI, 1.16 to 1.88; P = .002; OS: HR = 1.82; 95% CI, 1.10 to 3.01; P = .02), but it did not predict shorter RFS and OS in patients who received tamoxifen plus goserelin (RFS: HR = 0.99; 95% CI, 0.74 to 1.31; P = .9; OS: HR = 0.68; 95% CI, 0.40 to 1.15; P = .1). Tests for interaction between MRP1 expression and treatment were statistically significant for both RFS (P = .04) and OS (P = .006).
  
  
  CONCLUSIONS
  Our data suggest that MRP1 expression plays an important role in the clinical resistance to adjuvant CMF chemotherapy but does not seem to affect response to adjuvant endocrine treatment with tamoxifen plus goserelin. Thus, MRP1 may be a useful marker for the selection of patients with early-stage breast cancer for the appropriate adjuvant therapy after prospective confirmatory evaluation.
authors.affiliation: Department of Internal Medicine I, Clinical Division of Oncology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. martin.filipits@meduniwien.ac.at
authors.forename: Martin
authors.initials: M
authors.lastname: Filipits
authors.forename: Gudrun
authors.initials: G
authors.lastname: Pohl
authors.forename: Margaretha
authors.initials: M
authors.lastname: Rudas
authors.forename: Otto
authors.initials: O
authors.lastname: Dietze
authors.forename: Sigurd
authors.initials: S
authors.lastname: Lax
authors.forename: Renate
authors.initials: R
authors.lastname: Grill
authors.forename: Robert
authors.initials: R
authors.lastname: Pirker
authors.forename: Christoph C
authors.initials: CC
authors.lastname: Zielinski
authors.forename: Hubert
authors.initials: H
authors.lastname: Hausmaninger
authors.forename: Ernst
authors.initials: E
authors.lastname: Kubista
authors.forename: Hellmut
authors.initials: H
authors.lastname: Samonigg
authors.forename: Raimund
authors.initials: R
authors.lastname: Jakesz
mesh_terms: D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001317:Austria; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality*; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D018432:Drug Resistance, Multiple; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D017273:Goserelin / Q000627:therapeutic use; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000378:metabolism; D017697:Premenopause; D013629:Tamoxifen / Q000627:therapeutic use
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D003520:Cyclophosphamide; D005472:Fluorouracil; D017273:Goserelin; D008727:Methotrexate; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D013629:Tamoxifen; C421109:multidrug resistance-associated protein 1