PROGNOSTIC FACTORS IN N+ BREAST CANCER

Clin Cancer Res. 2010 Jun 24. [Epub ahead of print]
BCIRG001 Molecular Analysis: Prognostic Factors in Node-Positive Breast Cancer Patients Receiving Adjuvant Chemotherapy.
Dumontet C, Krajewska M, Treilleux I, Mackey JR, Martin M, Rupin M, Lafanechere L, Reed JC.

Faculté de Médecine Rockefeller, INSERM.
Abstract

PURPOSE: There are currently no validated factors predictive of response to taxanes in patients with breast cancer. We analysed specimens from patients included in the BCIRG 001 trial, a randomized study which demonstrated superiority of docetaxel/ doxorubicin/ cyclophosphamide over fluorouracil/doxorubicin/ cyclophosphamide as adjuvant therapy for node positive operable breast cancer in terms of disease free and overall survival.Experimental design: Immunohistochemical assessment of biological markers included histological 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 histological 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, Ki-67 protein were associated both with DFS and with OS while tau 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 protein expression in primary tumors of Ki-67 and P53 protein, as well as of the microtubule-related parameters tau 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.