Predictive and Prognostic Values of Tau and ERCC1 in Advanced Breast Cancer Patients Treated with Paclitaxel and Cisplatin

Shao, Yu‐Yun; Kuo, Kuan‐Ting; Hu, Fu‐Chang; Lu, Yen‐Shen; Huang, Chiun‐Sheng; Liau, Jau–Yu; Lee, Wei-Chung Allen; Hsu, Chiun; Kuo, Wun-Hon; Chang, King‐Jen; Lin, Ching‐Hung; Cheng, Ann‐Lii

doi:10.1093/jjco/hyp184

Cited by 30 publications

(28 citation statements)

References 31 publications

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“…However, this study is now the second cohort to fail to show an association between MAP-tau expression levels and response to taxane therapy in the metastatic setting. Although both studies [15] are relatively small, the lack of association in either case raises question regarding the value of measuring MAP-tau in large taxane trials.…”

Section: Discussionmentioning

confidence: 99%

“…In advanced breast cancer patients, an early study of MAP-tau expression found no prediction of benefit from taxane therapy [13]. However, two additional studies of advanced breast cancer patients found high MAP-tau expression predictive for response to paclitaxel [14,15] and a positive prognostic marker for improved overall survival [15]. …”

Section: Introductionmentioning

confidence: 99%

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Evaluation of prognostic and predictive value of microtubule associated protein tau in two independent cohorts

et al. 2011

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IntroductionMicrotubule associated proteins (MAPs) endogenously regulate microtubule stabilization and have been reported as prognostic and predictive markers for taxane response. The microtubule stabilizer, MAP-tau, has shown conflicting results. We quantitatively assessed MAP-tau expression in two independent breast cancer cohorts to determine prognostic and predictive value of this biomarker.MethodsMAP-tau expression was evaluated in the retrospective Yale University breast cancer cohort (n = 651) using tissue microarrays and also in the TAX 307 cohort, a clinical trial randomized for TAC versus FAC chemotherapy (n = 140), using conventional whole tissue sections. Expression was measured using the AQUA method for quantitative immunofluorescence. Scores were correlated with clinicopathologic variables, survival, and response to therapy.ResultsAssessment of the Yale cohort using Cox univariate analysis indicated an improved overall survival (OS) in tumors with a positive correlation between high MAP-tau expression and overall survival (OS) (HR = 0.691, 95% CI = 0.489-0.974; P = 0.004). Kaplan Meier analysis showed 10-year survival for 65% of patients with high MAP-tau expression compared to 52% with low expression (P = .006). In TAX 307, high expression was associated with significantly longer median time to tumor progression (TTP) regardless of treatment arm (33.0 versus 23.4 months, P = 0.010) with mean TTP of 31.2 months. Response rates did not differ by MAP-tau expression (P = 0.518) or by treatment arm (P = 0.584).ConclusionsQuantitative measurement of MAP-tau expression has prognostic value in both cohorts, with high expression associated with longer TTP and OS. Differences by treatment arm or response rate in low versus high MAP-tau groups were not observed, indicating that MAP-tau is not associated with response to taxanes and is not a useful predictive marker for taxane-based chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evaluation of prognostic and predictive value of microtubule associated protein tau in two independent cohorts

et al. 2011

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“…Microtubule associated protein (MAP) Tau binds to β-tubulin in the same place as paclitaxel and may consequently compete with this drug (15). Some studies focused on breast and gastric cancer revealed that patients with low expression of Tau protein benefit from paclitaxel therapy (16)(17)(18)(19)(20). Nevertheless, other studies, based on larger groups of breast cancer patients did not confirm these results (21,22).…”

Section: Introductionmentioning

confidence: 99%

Resistance to first line platinum paclitaxel chemotherapy in serous epithelial ovarian cancer: The prediction value of ERCC1 and Tau expression

Steffensen

Smoter

Waldstrøm

et al. 2014

International Journal of Oncology

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Abstract. In oncology, a rational approach to identify patients who are likely to benefit from therapy, already before initiation of treatment, is urgently required. Excision repair cross-complementation group 1 enzyme (ERCC1) has been proposed as a molecular predictor of clinical resistance to platinum-based chemotherapy. Other data suggest Tau protein expression as a predictor of clinical outcome in cancer patients treated with paclitaxel-based chemotherapy as low tau expression may render microtubules more vulnerable to paclitaxel. Therefore, the combination of ERCC1 and Tau may be a valuable predictor of sensitivity to platinum/paclitaxel treatment. The primary aim of the study was to investigate whether ERCC1 and Tau protein expression correlates with patient outcome in newly diagnosed epithelial ovarian cancer (EOC) patients. Formalin-fixed, paraffin-embedded tissue sections from 227 newly diagnosed EOC patients were used for immunohistochemical staining for ERCC1 and Tau proteins. All patients received standard first-line combination platinum and paclitaxel chemotherapy. The patients were divided in a training set of 84 patients and an independent validation cohort of 143 patients. Neither ERCC1 nor Tau expression was associated with clinical response or platinum resistance in both the training and validation sets. Patients with ERCC1-positive tumors had significantly shortened progression-free and overall survival compared to patients with ERCC1-negative tumors, p<0.00001 and p= 0.0006. In multivariate analysis ERCC1 also proved as an independent predictor of PFS and OS with HR of 3.86 and 1.98, respectively but the data could not be confirmed in the validation set. Tau expression was not associated with PFS or OS in this study. ERCC1 and Tau might serve as biomarkers of DNA repair and for paclitaxel sensitivity but the present study could not validate ERCC1 or Tau protein expression in tumors as pre-treatment tools to predict sensitivity to first-line platinum/paclitaxel chemotherapy.

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“…Sixty percent of Tau-negative expression showed favorable response (CR or partial response [PR]) to paclitaxel administration compared to 15% of Tau-positive expression. Shao et al14 analyzed Tau expression in 54 advanced breast cancer patients who received first-line chemotherapy of paclitaxel and cisplatin. Tau expression was significantly associated with lower overall response rate (CR or PR) (p=.02).…”

Section: Discussionmentioning

confidence: 99%

Microtubule-Associated Protein Tau, α-Tubulin and βIII-Tubulin Expression in Breast Cancer

Yoo

Jung

et al. 2013

Korean J Pathol

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BackgroundThe microtubule-associated protein Tau binds to both inner and outer surfaces of microtubules, leading to tubulin assembly and microtubule stabilization. The aim of this study was to evaluate the significance of Tau, α-tubulin, and βIII-tubulin expression in breast carcinoma and to assess their relationships with disease progression in the context of taxane treatment.MethodsImmunohistochemical expressions of Tau, α-tubulin, and βIII-tubulin were assessed in 183 breast cancer cases. Expression was correlated with clinicopathologic parameters, disease progression and overall survival.ResultsTau expression was correlated with lymph node metastasis and estrogen receptor (ER) positivity (p=.003 and p<.001, respectively). Loss of α-tubulin was significantly correlated with distant metastasis (p=.034). Loss of βIII-tubulin was correlated with lymph node metastasis and ER positivity (p=.004 and p<.001, respectively). In taxane-treated cases, Tau expression and loss of α-tubulin and βIII-tubulin expression were related to disease progression (p=.001, p=.028, and p=.030, respectively). Tau expression was associated with a worse survival rate in taxane-treated patients (p=.049).ConclusionsTau expression and loss of α-tubulin and βIII-tubulin expression were correlated with aggressive behavior in taxane-treated breast cancer. Further evaluation of Tau, α-tubulin and βIII-tubulin may be useful in predicting clinical behavior and seeking therapeutic measures in taxane-based chemotherapy for breast cancer.

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Predictive and Prognostic Values of Tau and ERCC1 in Advanced Breast Cancer Patients Treated with Paclitaxel and Cisplatin

Abstract: Tau expression but not excision repair cross-complementing 1 in advanced breast cancer predicts poor response to combination chemotherapy of paclitaxel and cisplatin. However, tau expression is significantly associated with longer overall survival.

Cited by 30 publications

References 31 publications

Evaluation of prognostic and predictive value of microtubule associated protein tau in two independent cohorts

Evaluation of prognostic and predictive value of microtubule associated protein tau in two independent cohorts

Resistance to first line platinum paclitaxel chemotherapy in serous epithelial ovarian cancer: The prediction value of ERCC1 and Tau expression

Microtubule-Associated Protein Tau, α-Tubulin and βIII-Tubulin Expression in Breast Cancer

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