Clinical role of multidrug resistance protein 1 expression in chemotherapy resistance in early-stage breast cancer: the Austrian Breast and Colorectal Cancer Study Group.
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.
Filipits
Martin
M
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
Pohl
Gudrun
G
Rudas
Margaretha
M
Dietze
Otto
O
Lax
Sigurd
S
Grill
Renate
R
Pirker
Robert
R
Zielinski
Christoph C
CC
Hausmaninger
Hubert
H
Kubista
Ernst
E
Samonigg
Hellmut
H
Jakesz
Raimund
R
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
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