4.5 Article

GSTP1 expression predicts poor pathological complete response to neoadjuvant chemotherapy in ER-negative breast cancer

Journal

CANCER SCIENCE
Volume 103, Issue 5, Pages 913-920

Publisher

WILEY
DOI: 10.1111/j.1349-7006.2012.02231.x

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Funding

  1. Promotion of Cancer Research (Japan) for the 3rd Term Comprehensive 10-Year Strategy for Cancer Control
  2. Pfizer
  3. Bristol-Myers Squibb

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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 similar to=similar to 123, stage IIIII) 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 similar to=similar to 0.009) among estrogen receptor (ER)-negative tumors but not among ER-positive tumors (P similar to=similar to 0.267). Multivariate analysis showed that GSTP1 was the only predictive factor for pCR (P similar to=similar to 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 similar to=similar to 0.002, P similar to

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