GSTP1 expression predicts poor pathological complete response to neoadjuvant chemotherapy in ER-negative breast cancer.
The purpose of the present study was to investigate the association of glutathione S-transferase P1 (GSTP1) expression with resistance to neoadjuvant paclitaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide (P-FEC) in human breast cancers. The relationship of GSTP1 expression and GSTP1 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. GSTP1 expression was determined using immunohistochemistry, GSTP1 promoter methylation index (MI) using bisulfite methylation assay and intrinsic subtypes using DNA microarray. The pathological complete response (pCR) rate was significantly higher in GSTP1-negative tumors (80.0%) than GSTP1-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 GSTP1 was the only predictive factor for pCR (P = 0.013) among ER-negative tumors. Luminal A, luminal B and HER2-enriched tumors showed a significantly lower GSTP1 positivity than basal-like tumors (P = 0.002, P < 0.001 and P = 0.009, respectively), while luminal A, luminal B and HER2-enriched tumors showed a higher GSTP1 MI than basal-like tumors (P = 0.076, P < 0.001 and P < 0.001, respectively). In conclusion, these results suggest the possibility that GSTP1 expression can predict pathological response to P-FEC in ER-negative tumors but not in ER-positive tumors. Additionally, GSTP1 promoter hypermethylation might be implicated more importantly in the pathogenesis of luminal A, luminal B and HER2-enriched tumors than basal-like tumors.
Department of Breast and Endocrine Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Tomohiro
T
Miyake
Takahiro
T
Nakayama
Yasuto
Y
Naoi
Noriaki
N
Yamamoto
Yoko
Y
Otani
Seung J
SJ
Kim
Kenzo
K
Shimazu
Atsushi
A
Shimomura
Naomi
N
Maruyama
Yasuhiro
Y
Tamaki
Shinzaburo
S
Noguchi
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D003520:Cyclophosphamide / Q000627:therapeutic use; D019175:DNA Methylation; D004352:Drug Resistance, Microbial; D019008:Drug Resistance, Neoplasm; D015251:Epirubicin / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D051549:Glutathione S-Transferase pi / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020360:Neoadjuvant Therapy; D017239:Paclitaxel / Q000008:administration & dosage; D011401:Promoter Regions, Genetic; D011960:Receptors, Estrogen / Q000378:metabolism*
D011960:Receptors, Estrogen; D015251:Epirubicin; D003520:Cyclophosphamide; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D017239:Paclitaxel; D005472:Fluorouracil