Microtubule-associated protein-tau is a bifunctional predictor of endocrine sensitivity and chemotherapy resistance in estrogen receptor-positive breast cancer
Microtubule-associated protein-tau is a bifunctional predictor of endocrine sensitivity and chemotherapy resistance in estrogen receptor-positive breast cancer
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DOI：
10.1158/1078-0432.ccr-06-2078
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发表时间：
2007-04-01
影响因子：
11.5
通讯作者：
Pusztai, Lajos
中科院分区：
文献类型：
--
作者：
Andre, Fabrice;Hatzis, Christos;Pusztai, Lajos
目的：乳腺癌患者的临床结局受癌症的转移能力及其对内分泌治疗和化疗的敏感性的影响。一个分子标志物可以是预后的结果或预测的治疗反应，或两者的组合。实验设计：我们分别研究了雌激素受体（ER）阳性的原发性乳腺癌在三个患者队列中的预后和预测值的RNA表达的tau蛋白。我们使用来自209名未经治疗的患者的基因表达数据来评估tau蛋白的纯预后价值，使用来自267名接受辅助他莫昔芬治疗的患者的数据来评估内分泌治疗的预测价值，使用来自82名接受术前紫杉醇治疗的患者的数据，然后使用5-氟尿嘧啶，多柔比星和环磷酰胺（紫杉醇/FAC）来评估化疗反应的预测价值。Wilcoxon秩和检验被用来比较不同的结果groups.Results之间的tau蛋白表达：较高的tau蛋白mRNA的表达显示边界非显着关联，在没有全身辅助治疗的情况下，预后较好。在接受他莫昔芬治疗的患者中，较高的tau mRNA表达与无复发显著相关（5年和10年，分别为P = 0.005和P = 0.05），表明内分泌治疗的预测价值。Tau蛋白在紫杉醇/FAC化疗后病理完全缓解的乳腺癌中的表达显著降低（P < 0.001）。相比之下，低tau表达识别了一部分ER阳性癌症，这些癌症单独使用他莫昔芬预后较差，并且可能从含紫杉烷的化疗中受益。
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 in RNA 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 m RNA 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 in RNA 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.