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. 2009 Sep 10;27(26):4287-92.
doi: 10.1200/JCO.2008.21.6887. Epub 2009 Aug 10.

Evaluation of microtubule-associated protein-Tau expression as a prognostic and predictive marker in the NSABP-B 28 randomized clinical trial

Lajos Pusztai  1 , Jong-Hyeon Jeong, Yun Gong, Jeffrey S Ross, Chungyeul Kim, Soonmyung Paik, Roman Rouzier, Fabrice Andre, Gabriel N Hortobagyi, Norman Wolmark, W Fraser Symmans
Affiliations

Evaluation of microtubule-associated protein-Tau expression as a prognostic and predictive marker in the NSABP-B 28 randomized clinical trial

Lajos Pusztai et al. J Clin Oncol. .

Abstract

Purpose: 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.

Conclusion: 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.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
Disease-free survival of all patients by treatment arm and Tau status. Kaplan-Meier survival curves are shown. Tau-low cases correspond to Tau-negative immunohistochemistry results. AC, doxorubicin and cyclophosphamide; ACT, AC and paclitaxel; RR, risk ratio.
Fig 2.
Fig 2.
Overall survival of all patients by treatment arm and Tau status. Kaplan-Meier survival curves are shown. Tau-low cases correspond to Tau-negative immunohistochemistry results. AC, doxorubicin and cyclophosphamide; ACT, AC and paclitaxel; RR, risk ratio.
Fig 3.
Fig 3.
Disease-free survival of estrogen receptor–positive patients by treatment arm and Tau status. Kaplan-Meier survival curves are shown. Tau-low cases correspond to Tau-negative immunohistochemistry results. AC, doxorubicin and cyclophosphamide; ACT, AC and paclitaxel; RR, risk ratio.
Fig 4.
Fig 4.
Disease-free survival of estrogen receptor–negative patients by treatment arm and Tau status. Kaplan-Meier survival curves are shown. Tau-low cases correspond to Tau negative immunohistochemistry results. AC, doxorubicin and cyclophosphamide; ACT, AC and paclitaxel; RR, risk ratio.
Fig A1.
Fig A1.
Overall survival of estrogen receptor–positive, Tau-negative patients by treatment arm. Kaplan-Meier survival curves are shown. AC, doxorubicin and cyclophosphamide; ACT, AC and paclitaxel; RR, risk ratio.
Fig A2.
Fig A2.
Overall survival of estrogen receptor–positive, Tau-positive patients by treatment arm. Kaplan-Meier survival curves are shown. AC, doxorubicin and cyclophosphamide; ACT, AC and paclitaxel; RR, risk ratio.
Fig A3.
Fig A3.
Overall survival of estrogen receptor–negative, Tau-negative patients by treatment arm. Kaplan-Meier survival curves are shown. AC, doxorubicin and cyclophosphamide; ACT, AC and paclitaxel; RR, risk ratio.
Fig A4.
Fig A4.
Overall survival of estrogen receptor–negative, Tau-positive patients by treatment arm. Kaplan-Meier survival curves are shown. AC, doxorubicin and cyclophosphamide; ACT, AC and paclitaxel; RR, risk ratio.
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