Evaluation of microtubule-associated protein-Tau expression as a prognostic and predictive marker in the NSABP-B 28 randomized clinical trial.
OBJECTIVE
We assessed Tau protein expression in primary breast cancer specimens of patients included in the National Surgical Breast and Bowel Project (NSABP) -B 28 clinical trial. Expression levels were correlated with disease-free survival (DFS) and overall survival (OS). Interaction between this marker and paclitaxel efficacy was also examined.


METHODS
Tissue microarrays were available for 1,942 patients (63% of all trial participants) who were randomly assigned to receive either four courses of doxorubicin and cyclophosphamide (AC) or AC followed by four courses of adjuvant paclitaxel chemotherapy. All patients who were hormone receptor positive received adjuvant endocrine therapy. Immunohistochemistry was used to measure Tau expression at M. D. Anderson Cancer Center blinded to clinical outcome. Correlation between Tau and OS and DFS was performed by the NSABP Biostatistical Center.


RESULTS
Forty-three percent of patients were Tau positive. Tau positivity correlated with estrogen receptor (ER) -positive status (P < .0001), lower histologic grade (P < .001), and lack of human epidermal growth factor receptor 2 (HER2) expression (P < .0001). In univariate analyses, Tau- and ER-positive status were both associated with better DFS and OS (P < .0001) whereas greater tumor size, high grade, lymph node- and HER2-positive status were each associated with worse DFS and OS (P < .0001). In multivariate analysis, the same variables except HER2 remained significant. There was no significant interaction between Tau expression and benefit from paclitaxel in the total population or among ER-positive or -negative patients.


CONCLUSIONS
High Tau protein expression is associated with better prognosis in patients treated with adjuvant anthracycline and paclitaxel chemotherapy and endocrine therapy, but there was no significant interaction between Tau expression and paclitaxel benefit.
Pusztai
Lajos
L
Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, PO Box 301439, Houston, TX 77230-1439, USA. lpusztai@mdanderson.org
Jeong
Jong-Hyeon
JH
Gong
Yun
Y
Ross
Jeffrey S
JS
Kim
Chungyeul
C
Paik
Soonmyung
S
Rouzier
Roman
R
Andre
Fabrice
F
Hortobagyi
Gabriel N
GN
Wolmark
Norman
N
Symmans
W Fraser
WF
D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000009:adverse effects; D004317:Doxorubicin / Q000009:adverse effects; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry / Q000706:statistics & numerical data; D053208:Kaplan-Meier Estimate; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D015999:Multivariate Analysis; D017239:Paclitaxel / Q000009:adverse effects; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016875:tau Proteins / Q000096:biosynthesis*
D018943:Anthracyclines; D014408:Biomarkers, Tumor; D003520:Cyclophosphamide; D004317:Doxorubicin; D047628:Estrogen Receptor alpha; D008869:Microtubule-Associated Proteins; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D016875:tau Proteins