Cyclin E expression in breast cancer:: predicting germline BRCA1 mutations, prognosis and response to treatment
Cyclin E expression in breast cancer:: predicting germline BRCA1 mutations, prognosis and response to treatment
复制标题
DOI：
10.1093/annonc/mdi149
复制
发表时间：
2005-05-01
影响因子：
50.5
通讯作者：
Foulkes, WD
中科院分区：
文献类型：
--
作者：
Chappuis, PO;Donato, E;Foulkes, WD
背景资料：细胞周期蛋白cyclin E水平升高，其抑制剂P27（Kip 1）水平降低，与乳腺癌预后不良有关。一些研究发现，乳腺癌易感基因BRCA 1的生殖系突变也与较低的生存率有关。细胞周期蛋白E/p27（Kip 1）水平，BRCA 1状态和结果之间的关系还没有研究detailed.Patients和方法：我们分析了一个历史队列的288德系犹太妇女谁被诊断为乳腺癌1980年和1995年之间，以前测试BRCA 1/2突变。免疫组化法检测细胞周期蛋白E（cyclin E）和p27（KiP 1）蛋白水平。乳腺癌特异性生存率（BCSS）是主要的结果测量。结果：中位随访时间为8年。30例肿瘤携带生殖系BRCA 1突变。与没有BRCA 1/2突变的患者相比，这些肿瘤更可能具有高细胞周期蛋白E蛋白水平[比值比（OR）9.5; P < 0.001]和低p27（Kip 1）蛋白水平（OR 2.8; P = 0.03）。高细胞周期蛋白E表达水平是BRCA 1种系突变的最强预测因子（多变量OR 4.7; P = 0.004）。单因素分析显示，高细胞周期蛋白E蛋白水平[相对危险度（RR）2.6; P < 0.001]和低p27（Kip 1）蛋白水平（RR 2.3; P = 0.006）是BCSS较差的重要预后因素。在考克斯多变量模型，高细胞周期蛋白E水平仍然是一个独立的指标，只有在亚组的患者谁没有接受化疗（P = 0.002）。结论：在这个种族限制的队列，高水平的细胞周期蛋白E是BRCA 1相关的乳腺癌的特征，是乳腺癌预后不良的标志物，特别是在没有辅助化疗。
Background: Elevated levels of the cell cycle protein cyclin E, and low levels of its inhibitor, P27(Kip1), have been associated with a poor prognosis following breast cancer. Some studies have found that germline mutations in the breast cancer susceptibility gene, BRCA1, are also associated with an inferior survival rate. The relationship between cyclin E/p27(Kip1) levels, BRCA1 status and outcome has not been studied in detail.Patients and methods: We analyzed a historical cohort of 288 Ashkenazi Jewish women who were diagnosed with breast cancer between 1980 and 1995 and were previously tested for BRCA1/2 mutations. Protein levels of cyclin E and p27(KiP1) were assessed by immunohistochemistry. Breast cancer-specific survival (BCSS) was the main outcome measured.Results: The median follow-up was 8 years. Thirty tumors carried germline BRCA1 mutations. These tumors were more likely to have high cyclin E protein levels [odds ratio (OR) 9.5; P < 0.001] and low p27(Kip1) protein levels (OR 2.8; P = 0.03) than tumors from patients without BRCA1/2 mutations. High cyclin E expression level was the strongest predictor of BRCA1 germline mutations (multivariate OR 4.7; P = 0.004). On univariate analysis, high cyclin E protein levels [relative risk (RR) 2.6; P < 0.001] and low p27(Kip1) protein levels (RR 2.3; P = 0.006) were significant prognostic factors for a poorer BCSS. In Cox multivariate models, high cyclin E levels remained an independent indicator of poor outcome only in the subgroup of patients who did not receive chemotherapy (P = 0.002).Conclusions: In this ethnically restricted cohort, a high level of cyclin E is a characteristic of BRCA1-related breast cancer, and is a marker of poor prognosis following breast cancer, particularly in the absence of adjuvant chemotherapy.