BCIRG 001 molecular analysis: prognostic factors in node-positive breast cancer patients receiving adjuvant chemotherapy.
OBJECTIVE
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).


METHODS
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.
Dumontet
Charles
C
INSERM 590, Faculté Rockefeller, 8 Avenue Rockefeller, Lyon, France. charles.dumontet@chu-lyon.fr
Krajewska
Maryla
M
Treilleux
Isabelle
I
Mackey
John R
JR
Martin
Miguel
M
Rupin
Mathieu
M
Lafanechère
Laurence
L
Reed
John C
JC
D000971:Antineoplastic Combined Chemotherapy Protocols; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D017326:Clinical Trials, Phase III as Topic; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000473:pathology; D015337:Multicenter Studies as Topic; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D043823:Taxoids / Q000008:administration & dosage
D014408:Biomarkers, Tumor; D043823:Taxoids; D000077143:Docetaxel; D003520:Cyclophosphamide; D005472:Fluorouracil