title: 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.affiliation: Department of Preventive Medicine, USC/Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA 90089-9176, USA.
authors.forename: Eunjung
authors.initials: E
authors.lastname: Lee
authors.forename: Peter
authors.initials: P
authors.lastname: Nichols
authors.forename: Susan
authors.initials: S
authors.lastname: Groshen
authors.forename: Darcy
authors.initials: D
authors.lastname: Spicer
authors.forename: Amy S
authors.initials: AS
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D004317:Doxorubicin / Q000627:therapeutic use; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D006360:Heat-Shock Proteins / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D008207:Lymphatic Metastasis; D008593:Menopause; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D011237:Predictive Value of Tests; D043823:Taxoids / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel
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