Bcirg 001 Molecular Analysis: Identification Of Prognostic Factors In Patients (Pts) Receiving Adjuvant Therapy For Node-Positive (N Plus ) Breast Cancer (Bc)

525 Background: BCIRG 001 (1,491 pts) demonstrated significant superiority of docetaxel/doxorubicin/cyclophosphamide (TAC) over fluorouracil/doxorubicin/cyclophosphamide (FAC) given as adjuvant therapy for N+ operable BC in terms of disease-free survival (DFS) and overall survival (OS) (Martin et al, N Eng J Med, 2005). This ancillary study was aimed to identify tumor-associated factors related to DFS and OS. Methods: Formalin-fixed primary tumors from pts in BCIRG 001 were analysed by immunohistochemistry. Protocol- specified assessment of histological grade (GR), tumor size (TS), estrogen (ER) and progesterone receptors (PR), lymph node status (LN), HER2, MUC1, Mib, p53, Bcl-2, Bax, Bcl-X, Bag-1, tubulin β isotypes II, III and IV, tau protein and detyrosinated a tubulin was performed. Parameters were scored as the percentage of positive cells and analysed as lower or greater than median values. The samples were randomly split into training (2/3) and validation (1/3) sets. Associations between selected parameters and DFS or OS were tested through univariate analyses using the Kaplan Meier method (log-rank test) on the training set. A backward stepwise Cox regression analysis was performed to identify the final model of prognostic factors on the training set. Multivariate analyses were applied to the validation set. Results: 1,350 samples were split into a training (n=906) and a validation (n=444) set. In univariate GR, TS, LN, ER and PR, Mib, tau protein and HER2 were correlated with DFS in both sets. In multivariate ER, PR, TS, LN, Mib (all p<0.01) and tau (p=0.043) were significantly associated with DFS in the training set. In univariate GR, TS, LN, ER and PR, Mib, MUC1, Bcl-2, tubulin III and IV and tau were correlated with OS in both sets, with a trend for p53. In multivariate ER, TS, LN, Mib, p53 (all p<0.01) and PR (p=0.028) were independently correlated with OS in the training set. Conclusions: These data suggest that tau and p53 are independent markers of DFS and OS, respectively, while Mib is correlated with both DFS and OS in pts receiving these forms of adjuvant chemotherapy for N+ BC. Complementary analyses will be presented. No significant financial relationships to disclose.