PURPOSE: There are currently no validated factors predictive of response to taxanes in patients with breast cancer. We analyzed specimens from patients included in the Breast Cancer International Research Group (BCIRG) 001 trial, a randomized study which showed the superiority of docetaxel/doxorubicin/cyclophosphamide over fluorouracil/doxorubicin/cyclophosphamide as adjuvant therapy for node-positive operable breast cancer in terms of disease-free survival (DFS) and overall survival (OS). EXPERIMENTAL DESIGN: Immunohistochemical assessment of biological markers included histologic grade, tumor size, estrogen and progesterone receptors, lymph node status, HER2, MUC1, Ki-67/MIB-1, p53, Bcl-2, Bax, Bcl-XL, BAG-1, beta-tubulin isotypes II, III and IV, tau protein, and detyrosinated alpha tubulin. Associations between selected parameters and survival were tested through univariate analyses, then completed with multivariate analyses and a bootstrap resampling technique. RESULTS: In univariate analysis histologic grade, tumor size, number of involved nodes, estrogen and progesterone receptor status, p53, Ki-67, tubulin III, and tau protein were associated both with DFS and with OS. In multivariate analysis estrogen and progesterone receptors, tumor size, number of involved nodes, and Ki-67 protein were associated both with DFS and with OS, whereas tau protein levels were correlated with DFS and tubulin III and P53 were correlated with OS. No interaction was observed between Ki-67 and treatment allocation. CONCLUSIONS: We conclude that the expression in primary tumors of Ki-67 and p53 protein, as well as of the microtubule-related parameters tau protein and tubulin III, are independent prognostic factors in patients receiving adjuvant chemotherapy for node-positive breast cancer but are not predictive of benefit from docetaxel-containing adjuvant chemotherapy. (c) 2010 AACR.
RCT Entities:
PURPOSE: There are currently no validated factors predictive of response to taxanes in patients with breast cancer. We analyzed specimens from patients included in the Breast Cancer International Research Group (BCIRG) 001 trial, a randomized study which showed the superiority of docetaxel/doxorubicin/cyclophosphamide over fluorouracil/doxorubicin/cyclophosphamide as adjuvant therapy for node-positive operable breast cancer in terms of disease-free survival (DFS) and overall survival (OS). EXPERIMENTAL DESIGN: Immunohistochemical assessment of biological markers included histologic grade, tumor size, estrogen and progesterone receptors, lymph node status, HER2, MUC1, Ki-67/MIB-1, p53, Bcl-2, Bax, Bcl-XL, BAG-1, beta-tubulin isotypes II, III and IV, tau protein, and detyrosinated alpha tubulin. Associations between selected parameters and survival were tested through univariate analyses, then completed with multivariate analyses and a bootstrap resampling technique. RESULTS: In univariate analysis histologic grade, tumor size, number of involved nodes, estrogen and progesterone receptor status, p53, Ki-67, tubulin III, and tau protein were associated both with DFS and with OS. In multivariate analysis estrogen and progesterone receptors, tumor size, number of involved nodes, and Ki-67 protein were associated both with DFS and with OS, whereas tau protein levels were correlated with DFS and tubulin III and P53 were correlated with OS. No interaction was observed between Ki-67 and treatment allocation. CONCLUSIONS: We conclude that the expression in primary tumors of Ki-67 and p53 protein, as well as of the microtubule-related parameters tau protein and tubulin III, are independent prognostic factors in patients receiving adjuvant chemotherapy for node-positive breast cancer but are not predictive of benefit from docetaxel-containing adjuvant chemotherapy. (c) 2010 AACR.
Authors: Bruno Coudert; Bernard Asselain; Mario Campone; Marc Spielmann; Jean-Pascal Machiels; Frédérique Pénault-Llorca; Daniel Serin; Christelle Lévy; Gilles Romieu; Jean-Luc Canon; Hubert Orfeuvre; Gilles Piot; Thierry Petit; Guy Jerusalem; Bruno Audhuy; Corinne Veyret; Marc Beauduin; Jean-Christophe Eymard; Anne-Laure Martin; Henri Roché Journal: Oncologist Date: 2012-05-18
Authors: Jocelyne Jacquemier; Jean-Marie Boher; Henri Roche; Benjamin Esterni; Daniel Serin; Pierre Kerbrat; Fabrice Andre; Pascal Finetti; Emmanuelle Charafe-Jauffret; Anne-Laure Martin; Mario Campone; Patrice Viens; Daniel Birnbaum; Frédérique Penault-Llorca; François Bertucci Journal: Breast Cancer Res Date: 2011-11-01 Impact factor: 6.466