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Clinical Role of Multidrug Resistance Protein 1 Expression in Chemotherapy Resistance in Early-Stage Breast Cancer: The Austrian Breast and Colorectal Cancer Study Group

From the Departments of Internal Medicine I, Pathology, Surgery, and Gynecology, Medical University of Vienna, Vienna; Department of Pathology and Third Medical Department, Salzburg Hospital, Salzburg; Departments of Pathology and Internal Medicine, University of Graz, Graz; and Department of Pathology-Histology, Hanusch Medical Center, Vienna, Austria

Address reprint requests to Martin Filipits, PhD, Department of Internal Medicine I, Clinical Division of Oncology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria; e-mail: martin.filipits{at}meduniwien.ac.at

PURPOSE: 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.

PATIENTS AND 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).

CONCLUSION: 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.

This study was supported by a grant from the Austrian Science Fund (Project No. P15377) and the Center of Excellence in Clinical and Experimental Oncology of the Medical University of Vienna.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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