Investigation of MRP-1 protein and MDR-1 P-glycoprotein expression in invasive breast cancer: a prognostic study

Abstract

The efficacy of breast cancer treatment is limited by the development of resistance to various chemotherapeutic agents. We conducted a retrospective study of the expression of 2 drug resistance efflux pumps, MRP‐1 and MDR‐1 Pgp, in 177 invasive breast carcinomas. Immunohistochemical expression of these proteins was correlated with clinicopathologic characteristics as well as relapse‐free survival (RFS) and overall survival (OS) times. MDR‐1 Pgp was associated strongly with higher histologic grade (grade III). A highly significant association was shown between MDR‐1 Pgp and MRP‐1 expression (p < 0.01), 47.4% of patients expressing both proteins; MRP‐1 was expressed in approximately 61% of patients and MDR‐1, in approximately 66% of patients. No association was shown in the overall group between either MDR‐1 Pgp or MRP‐1 and any of the other clinicopathologic features. Kaplan‐Meier analysis revealed that in a subset of patients with either high‐grade (grade III) stage 1 (node‐negative) or stage 2 (node‐positive) tumours who were treated with surgery followed by adjuvant chemotherapy, MRP‐1 expression in <25% of tumour cells at diagnosis was significantly associated with improved RFS (p < 0.02) and OS (p < 0.02). Using multivariate analysis, MRP‐1 expression in <25% of tumour cells at diagnosis was identified as an independent, significant prognostic factor for RFS (p < 0.01) and OS (p < 0.01) in this patient group but not in other groups. In this subgroup, no significant correlation was observed between expression of MDR‐1 Pgp and MRP‐1. While the number of patients with high‐grade tumours treated with adjuvant chemotherapy was small and further confirmatory research is warranted, it appears that assessment of MRP‐1 expression at diagnosis may offer useful prognostic information in subgroups of patients with stage 1 or stage 2 high‐grade tumours who receive CMF‐based adjuvant chemotherapy. Given the known substrate specificities of MRP‐1, any mechanistic relationship between MRP‐1 expression and CMF resistance remains unclear. No association was shown between MDR‐1 Pgp expression and either RFS or OS time in any subgroup of patients.