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GSTP 1 expression predicts poor pathological complete response to neoadjuvant chemotherapy in ER‐negative breast cancer
Open accessAbstract
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)
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“Comparison of SLFN11 transcript levels in baseline (pre-treatment) tumor biopsy specimens showed that patients with CR had significantly higher SLFN11 expression than those that did not (p = 0.045) (Fig 4A).”
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Metadata
- Authors
- Miyake, T., Nakayama, T., Naoi, Y., Yamamoto, N., Otani, Y., Kim, S. J., Shimazu, K., Shimomura, A., Maruyama, N., Tamaki, Y., & Noguchi, S.
- Affiliations
- The University of Osaka (JP)
- Sysmex (Japan) (JP)
- Corresponding author
- Noguchi, Shinzaburo
- Venue
- Cancer Science
- Publisher
- Wiley
- Published
- 2012-03
- Volume
- 103
- Issue
- 5
- Pages
- 913-920
- ISSN
- 1347-9032 (ISSN-L)
- 1349-7006
- PMC
- PMC7659189
- OpenAlex
- W2051483759
- Cited by
- 146
- References
- 37
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 5 · 2023: 11 · 2022: 10 · 2021: 17 · 2020: 18 · 2019: 10 · 2018: 16 · 2017: 13 · 2016: 6 · 2015: 11 · 2014: 7 · 2013: 7 · 2012: 3
- FWCI
- 2.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Science (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
- Health Sciences › Medicine › Pathology and Forensic Medicine › Breast Lesions and Carcinomas
- Keywords
- GSTP1, glutathione S-transferase pi, estrogen receptor-negative breast cancer, neoadjuvant chemotherapy, pathological complete response, paclitaxel, FEC chemotherapy, predictive biomarkers, breast cancer intrinsic subtypes, basal-like breast cancer, luminal A, luminal B, HER2-enriched breast cancer
- MeSH terms
- Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Cyclophosphamide, Drug Resistance, Microbial, Female, Fluorouracil, Humans, Promoter Regions, Genetic, Receptors, Estrogen, Epirubicin, Paclitaxel, Drug Resistance, Neoplasm, DNA Methylation, Neoadjuvant Therapy, Glutathione S-Transferase pi
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