Prognostic impact of multidrug resistance gene expression on the management of breast cancer in the context of adjuvant therapy based on a series of 171 patients

Abstract

Study of the prognostic impact of multidrug resistance gene expression in the management of breast cancer in the context of adjuvant therapy. This study involved 171 patients treated by surgery, adjuvant chemotherapy7radiotherapy7hormonal therapy (mean follow-up: 55 months). We studied the expression of multidrug resistance gene 1 (MDR1), multidrug resistance-associated protein (MRP1), and glutathione-S-transferase P1 (GSTP1) using a standardised, semiquantitative rt -PCR method performed on frozen samples of breast cancer tissue. Patients were classified as presenting low or high levels of expression of these three genes. rt-PCR values were correlated with T stage, N stage, Scarff -Bloom -Richardson (SBR) grade, age and hormonal status. The impact of gene expression levels on 5-year disease-free survival (DFS) and overall survival (OS) was studied by univariate and multivariate Cox analysis. No statistically significant correlation was demonstrated between MDR1, MRP1 and GSTP1 expressions. On univariate analysis, DFS was significantly decreased in a context of low GSTP1 expression (P ¼ 0.0005) and high SBR grade (P ¼ 0.003), size X5 cm (P ¼ 0.038), high T stage (P ¼ 0.013), presence of intravascular embolus (P ¼ 0.034), and 43 N þ (P ¼ 0.05). On multivariate analysis, GSTP1 expression and the presence of ER remained independent prognostic factors for DFS. GSTP1 expression did not affect OS. The levels of MDR1 and MRP1 expression had no significant influence on DFS or OS. GSTP1 expression can be considered to be an independent prognostic factor for DFS in patients receiving adjuvant chemotherapy for breast cancer.

GSTP1 Promoter Haplotypes Affect DNA Methylation Levels and Promoter Activity in Breast Carcinomas

“…This is in concordance with previous reports where the absence of GSTP1 protein expression correlated with improved survival in invasive breast cancer samples (10,29) and colorectal cancer (11). In contrast, other studies related low GSTP1 expression or GSTP1 hypermethylation to decreased survival and poor prognosis (15,30). The difference between the results might be attributable to the molecular diversity in human breast cancer as well as differences in the received adjuvant therapy.…”

MRP1 Overexpression Determines Poor Prognosis in Prospectively Treated Patients with Localized High-Risk Soft Tissue Sarcoma of Limbs and Trunk Wall: An ISG/GEIS Study

“…Similarly, the expression of MRP1 was associated with an increased risk of failure in cases with small tumors, in node-negative tumors and in node-positive patients in a retrospective series of patients with localized breast cancer, who received adjuvant systemic chemotherapy based on MRP1 substrates such as cyclophosphamide and methotrexate (26). Nevertheless, another study found a statistically significant relationship of GST, but not MRP1, with disease-free survival in patients with localized breast cancer treated with adjuvant chemotherapy (27).…”

Association between GSTP1 Genotypes and Hormone Receptor Phenotype in Invasive Ductal Carcinomas of Breast

“…However, to date the results are still somewhat controversial and may vary from population to population. (Gilbert et al, 1993;Silvestrini et al, 1997;Buser et al, 1997;Helzlsouer et al, 1998;Millikan et al, 2000;Mitrunen et al, 2001;Gudmundsdottir et al, 2001;Huang et al, 2003;Egan et al, 2004;Sreenath et al, 2005;Moureau-Zabotto et al, 2006;Unlu et al, 2008;Saxena et al, 2009;Arun et al, 2010;Pongtheerat et al, 2011;Zhang et al, 2011;Ramalhinho et al, 2011;Aguiar et al, 2012;Ramalhinho et al, 2012;Saxena et al, 2013;Khabaz, 2014;Rodríguez et al, 2014).…”

“…Many previous studies revealed GSTP1 polymorphism has no correlation with clinical and pathologic tumor characteristics (Buser et al, 1997;Huang et al, 2003) only a few studies showed an inverse correlation with ER (Gilbert et al, 1993;Silvestrini et al, 1997;Moureau-Zabotto et al, 2006). Furthermore, two studies of Pongtheerat and colleagues reported that GSTP1 polymorphism was unrelated to increased risk of breast cancer, but found an inverse relationship between GSTP1 genotype and progesterone receptor protein (Pongtheerat et al, 2009;Pongtheerat et al, 2011), and positive correlation with better tumor differentiation and grade (Cairns et al, 1992;Haas et al, 2006).…”

“…Many studies investigated the possible link between GSTP1 polymorphisms and breast cancer risk, and have shown conflicting results (Gilbert et al, 1993;Silvestrini et al, 1997;Buser et al, 1997;Helzlsouer et al, 1998;Millikan et al, 2000;Mitrunen et al, 2001;Gudmundsdottir et al, 2001;Huang et al, 2003;Egan et al, 2004;Sreenath et al, 2005;Moureau-Zabotto et al, 2006;Unlu et al, 2008;Saxena et al, 2009;Arun et al, 2010;Pongtheerat et al, 2011;Zhang et al, 2011;Ramalhinho et al, 2011;Aguiar et al, 2012;Ramalhinho et al, 2012;Khabaz, 2014;Rodríguez et al, 2014). Many previous studies revealed GSTP1 polymorphism has no correlation with clinical and pathologic tumor characteristics (Buser et al, 1997;Huang et al, 2003) only a few studies showed an inverse correlation with ER (Gilbert et al, 1993;Silvestrini et al, 1997;Moureau-Zabotto et al, 2006).…”