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https://doi.org/10.1200/jco.2008.26.15_suppl.616
Copy DOIJournal: Journal of Clinical Oncology | Publication Date: May 20, 2008 |
Citations: 1 |
616 Background: The identification of predictive biomarkers for the efficacy of adjuvant treatments could allow to better tailor adjuvant treatments. We evaluated the predictive value of MRP2, bcl2, topoisomerase IIα (Topo IIα) expression and p53 status for the efficacy of adjuvant anthracyclines (A)-based chemotherapy. Methods: Tumor samples from 823 patients included at Institut Gustave Roussy (IGR) in two randomized trials comparing an A-based chemotherapy with no treatment were used to perform a tissue-array. Chemotherapy consisted of 5FU (500mg/m2), farmorubicine (90% of patients) or doxorubicin (50 mg/m2) and cyclophosphamide (500 mg/m2) (D1=D28) for 6 cycles. Immunostainings (cut-off: >10% stained cells) were performed for MRP2 (M2III-6; 1:300; Alexis), p53 ( DO-7; 1:50; Dako), bcl2 (124; 1:50; Dako), and Topo IIα (KI-S1; 1:5000; Chemicon). We previously reported predictive values of ER, HER2 expression and molecular subclassification using the same tissue-array (Conforti, Annals of Oncology, 2007). Results: After a median follow-up of 10 years, 174 patients (22%) have presented a relapse and 186 patients (24%) died. Chemotherapy improved DFS (HR = 0.77, 95% CI: 0.63- 0.9), but not OS (HR = 0.88, 95% CI: 0.66–1.1). A positive staining for MRP2, p53, Topo IIα and bcl2 was observed in 122 (16%), 157 (20%), 267 (35%) and 251 (34%) assessable samples respectively. P53 and Topo IIα were more frequently expressed in patients with basal-like (51% and 53%) or HER2-overexpressing tumors (44% and 57%), as compared to other groups (HER2- and nonbasal BC) (11% and 28%). Bcl2 was more frequently positive in patients with luminal-like breast cancer (47% versus 16%, p<0.01). No significant interaction was observed between the four biomarkers expression and treatment efficacy for both DFS and OS (adjusted p values for interaction ranged between 0.30 and 0.85). Conclusions: In this study, we did not detect significant interaction between MRP2, p53, bcl2 and Topo Iia expressions and treatment efficacy. Nevertheless, such study cannot exclude a possible interaction with a higher number of events or different methods (DNA sequencing for p53 mutations and lower dilution [1:200] for S1 Ab). No significant financial relationships to disclose.
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