GRP78 as potential predictor for breast cancer response to adjuvant taxane therapy.

Abstract

Few predictive markers exist for response to adjuvant chemotherapy in breast cancer. The 78-kDa glucose-regulated protein (GRP78) is a potent antiapoptotic factor, conferring drug resistance. Recently, we reported that high GRP78 expression in breast cancer specimens predicts a shorter recurrence-free survival in patients who received doxorubicin-based adjuvant chemotherapy. Interestingly, the opposite effect was observed in 25 patients who additionally received a taxane. To confirm this potentially paradigm shifting finding, we investigated whether GRP78 is associated with recurrence-free survival in an independent cohort of taxane-treated breast cancer patients. Immunohistochemical staining of GRP78 was performed on archival paraffin-embedded formalin-fixed tumor specimens obtained from 48 female breast cancer patients before chemotherapy treatment. These patients received doxorubicin and cyclophosphamide, followed by paclitaxel or docetaxel on a clinical trial. GRP78 expression level was evaluated by a pathologist, masked to all clinical and outcome data. Association between GRP78 expression and recurrence-free survival was evaluated. GRP78 positivity predicts a better recurrence-free survival, independent of other prognostic factors [hazard ratio (HR) for moderate positivity: 0.40 (95% confidence interval (CI): 0.087-1.83); HR for strong positivity: 0.16 (95% CI: 0.018-1.50); p(trend) = 0.053]. In a pooled analysis with the previous 25 patients, almost identical HRs were obtained with p(trend) = 0.024. This provides further evidence that GRP78 is a potential independent predictor for response to taxane-based adjuvant chemotherapy in breast cancer.

• Authors: Eunjung Lee, Peter Nichols, Susan Groshen, Darcy Spicer, Amy S Lee
• Journal: International journal of cancer (Int J Cancer) Vol. 128 Issue 3 Pg. 726-31 (Feb 01 2011) ISSN: 1097-0215 [Electronic] United States
• PMID: 20473863 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Endoplasmic Reticulum Chaperone BiP
• HSPA5 protein, human
• Heat-Shock Proteins
• Taxoids
• Docetaxel
• Doxorubicin
• Cyclophosphamide
• Paclitaxel

Topics

• Adult
• Aged
• Analysis of Variance
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers (analysis)
• Breast Neoplasms (drug therapy, genetics, pathology)
• Cyclophosphamide (administration & dosage)
• Docetaxel
• Doxorubicin (therapeutic use)
• Endoplasmic Reticulum Chaperone BiP
• Female
• Heat-Shock Proteins (analysis, metabolism)
• Humans
• Lymphatic Metastasis
• Menopause
• Middle Aged
• Multivariate Analysis
• Neoplasm Staging
• Paclitaxel (administration & dosage)
• Predictive Value of Tests
• Taxoids (administration & dosage, therapeutic use)
• Treatment Outcome