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Microtubule-Associated Protein-tau is a Bifunctional Predictor of Endocrine Sensitivity and Chemotherapy Resistance in Estrogen Receptor–Positive Breast Cancer

Authors' Affiliations: ¹ Breast Cancer Unit and Translational Research Unit, UPRES03535, Institut Gustave Roussy, Villejuif, France; Departments of ² Breast Medical Oncology, ³ Pathology, and ⁴ Biostatistics and Applied Mathematics, University of Texas M. D. Anderson Cancer Center, Houston, Texas; ⁵ Nuvera Biosciences, Inc., Woburn, Massachusetts, and ⁶ Institut Jules Bordet, Brussels, Belgium

Requests for reprints: Lajos Pusztai, Department of Breast Medical Oncology, Unit 1354, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-1439. Phone: 713-792-2817; Fax: 713-794-4385; E-mail: lpusztai{at}mdanderson.org.

Purpose: The clinical outcome for patients with breast cancer is influenced by the metastatic competence of the cancer and its sensitivity to endocrine therapy and chemotherapy. A molecular marker may be prognostic of outcome or predictive of response to therapy, or a combination of both.

Experimental Design: We examined separately the prognostic and predictive values of tau mRNA expression in estrogen receptor (ER)–positive primary breast cancers in three patient cohorts. We used gene expression data from 209 untreated patients to assess the pure prognostic value of tau, data from 267 patients treated with adjuvant tamoxifen to assess predictive value for endocrine therapy, and data from 82 patients treated with preoperative paclitaxel followed by 5-fluorouracil, doxorubicin, and cyclophosphamide (paclitaxel/FAC) to assess predictive value for chemotherapy response. Wilcoxon rank sum test was used to compare tau expression between different outcome groups.

Results: Higher tau mRNA expression showed borderline nonsignificant association with better prognosis in the absence of systemic adjuvant therapy. Higher tau mRNA expression was significantly associated with no recurrence (at 5 and 10 years, P = 0.005 and P = 0.05, respectively) in patients treated with tamoxifen, indicating a predictive value for endocrine therapy. Tau expression was significantly lower in patients who achieved pathologic complete response to paclitaxel/FAC chemotherapy (P < 0.001).

Conclusion: This study suggests that high tau mRNA expression in ER-positive breast cancer indicates an endocrine-sensitive but chemotherapy-resistant disease. In contrast, low tau expression identifies a subset of ER-positive cancers that have poor prognosis with tamoxifen alone and may benefit from taxane-containing chemotherapy.

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