GSTP 1 expression predicts poor pathological complete response to neoadjuvant chemotherapy in ER‐negative breast cancer

Abstract

The purpose of the present study was to investigate the association of glutathione S‐transferase P 1 (GSTP 1) expression with resistance to neoadjuvant paclitaxel followed by 5‐fluorouracil/epirubicin/cyclophosphamide (P‐FEC) in human breast cancers. The relationship of GSTP 1 expression and GSTP 1 promoter hypermethylation with intrinsic subtypes was also investigated. In this study, primary breast cancer patients (n = 123, stage II–III) treated with neoadjuvant P‐FEC were analyzed. Tumor samples were obtained by vacuum‐assisted core biopsy before P‐FEC. GSTP 1 expression was determined using immunohistochemistry, GSTP 1 promoter methylation index (MI) using bisulfite methylation assay and intrinsic subtypes using DNA microarray. The pathological complete response (pCR) rate was significantly higher in GSTP 1‐negative tumors (80.0%) than GSTP 1‐positive tumors (30.6%) (P = 0.009) among estrogen receptor (ER)‐negative tumors but not among ER‐positive tumors (P = 0.267). Multivariate analysis showed that GSTP 1 was the only predictive factor for pCR (P = 0.013) among ER‐negative tumors. Luminal A, luminal B and HER 2‐enriched tumors showed a significantly lower GSTP 1 positivity than basal‐like tumors (P = 0.002, P < 0.001 and P = 0.009, respectively), while luminal A, luminal B and HER 2‐enriched tumors showed a higher GSTP 1 MI than basal‐like tumors (P = 0.076, P < 0.001 and P < 0.001, respectively). In conclusion, these results suggest the possibility that GSTP 1 expression can predict pathological response to P‐FEC in ER‐negative tumors but not in ER‐positive tumors. Additionally, GSTP 1 promoter hypermethylation might be implicated more importantly in the pathogenesis of luminal A, luminal B and HER 2‐enriched tumors than basal‐like tumors. (Cancer Sci 2012; 103: 913–920)